Comparison of clinical outcome and patency of Gore-Viatorr and …repository-tnmgrmu.ac.in/9029/1/200801118manisha... · 2018-07-31 · Dr. Manisha Sheshrao Mane Post graduate student

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Comparison of clinical outcome and patency of

Gore-Viatorr and Niti-S stents used in

Transjugular intrahepatic portosystemic shunt

(TIPS)

A dissertation submitted in partial fulfillment of MD Radiodiagnosis (Branch VIII)

examination of the Tamil Nadu Dr. M.G.R Medical University, Chennai to be held in

May 2018

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DECLARATION

I declare that the dissertation entitled “Comparison of clinical outcome and patency of

Gore-Viatorr and Niti-S stents used in Transjugular intrahepatic portosystemic shunt

(TIPS)” is my original work done in partial fulfillment of the requirement for MD

Radiodiagnosis (Branch VIII) Degree Examination of the Tamil Nadu Dr. M.G.R

Medical University, Chennai to be held in May 2018

Dr. Manisha Sheshrao Mane

Post graduate student (MD Radiodiagnosis)

Department of Radiodiagnosis

Christian Medical College

Vellore -632004

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CERTIFICATE





Medical University, Chennai to be held in May 2018.

Guide

Dr. Munawwar Ahmed

Associate Proffesor,

Christian medical college,

Vellore.

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CERTIFICATE






Head of the Department

Dr. Shridhar Gibitoke

Professor

Department of Radiodiagnosis


Vellore – 632004

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CERTIFICATE






Dr. Anna Pulimood

Principal


Vellore – 632004

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PLAGIARISM CERTIFICATE

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ACKNOWLEDGEMENTS

I wish to express my deep gratitude to my guide Dr. Munawwar Ahmed,

AssociateProfessor, Department of Radiology, Christian Medical College and

Hospital, Vellore for all his wisdom and expert guidance throughout the work on my

dissertation.

I am grateful to Dr. Shyam Kumar for is expert guidance, hard work and

encouragement throughout the work on my dissertation.

I am also grateful to Dr. Vinu, Dr. Ashwin from the Department of Radiology,

Christian Medical College and Hospital, Vellore and Dr. CE.E.Eapen, Head and

professor of Gastroenterology and Hepatology, Dr.Uday Zackariah, Professor and

acting head of Hepatology, Dr.Ashish Goel, Professor professor in the Department of

Hepatology, Christian Medical College and Hospital, Vellore for their advice,

support, encouragement and valuable inputs in

carrying out this study.

I wish to specially thank all radiographers and nursing staff posted in DSA Room 22

.

Dr. Jayaseelan, Ms.Visalash, Miss Jothi for her timely help with statistics and data

analysis.

CMC Vellore and all my teachers, for making this study and this course a reality.

I am grateful most importantly to all the patients without whom this study would not

have been possible.

My family, friends and colleagues for their love, constant support and encouragement.

And to the Lord Almighty for all his blessings, throughout my life

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Table of Contents INTRODUCTION: .................................................................................................................................... 13

AIM: ....................................................................................................................................................... 16

OBJECTIVES: .......................................................................................................................................... 16

REVIEW OF LITERATURE: ....................................................................................................................... 17

MATERIALS AND METHODS: ................................................................................................................. 37

SUMMARY OF METHODOLOGY: ........................................................................................................... 51

RESULTS ................................................................................................................................................ 53

SUMMARY OF RESULTS:........................................................................................................................ 83

DISCUSSION:.......................................................................................................................................... 84

LIMITATIONS: ........................................................................................................................................ 91

CONCLUSIONS: ...................................................................................................................................... 92

REFERENCES: ......................................................................................................................................... 93

ANNEXURES: ......................................................................................................................................... 96

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INTRODUCTION:

TIPS (Transjugular intrahepatic portosystemic shunt) is an image guided intrahepatic

parenchymal shunt created between portal vein and systemic circulation [hepatic vein

or inferior vena cava] (1).

Creation of this shunt helps in diverting blood flow away from portal system and

reduces the portal pressure. Reduction of the portal pressure decreases the risk of

variceal bleeding, recurrent ascites and hydrothorax. Thus TIPS is a useful modality

for treating complications of portal hypertension like refractory ascites, acute or

recurrent variceal haemorrhage, hepatic hydrothorax, hepato-renal syndrome and

hepatopulmonary syndrome. It is also useful for treating Budd Chiari and act as bridge

to liver transplant (1).

If the intrahepatic shunt is created between portal vein and hepatic vein the procedure

is called TIPS (Transjugular intrahepatic portosystemic shunt) as shown in figure

1a.(1). If instead of hepatic vein inferior vena cava is punctured directly the procedure

is called as Direct intrahepatic portosystemic shunt as shown in figure 1b.

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Figure 1a: Schematic representation of TIPS

Figure 1: Schematic representation of TIPS

FIGURE 1b: Schematic representation of Direct TIPS

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In the early years bare metal stents were used, higher shunt failure rate was the major

drawback of these stents. With the introduction of covered stents especially Gore

Viatorr, shunt patency significantly improved. Which in turn improved the symptom

free survival time and decreased the morbidity (2).

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AIM:

Comparison of clinical outcome and patency of Gore-Viatorr and Niti-S stents

used in Transjugular intrahepatic portosystemic shunt (TIPS).

OBJECTIVES:

1) To compare primary patency at 3 months and secondary patency rates at 24 months

of Gore-Viatorr and Niti-S stents

2) Which stent has the best primary patency rate?

3) Compare clinical outcome of Gore-Viatorr and Niti-S stents

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REVIEW OF LITERATURE:

History and evolution:

TIPS(Transjugular intrahepatic portosystemic shunt) was first introduced by Rosch et

al in 1969 (3).

In 1982, Colaptino performed this procedure in a cirrhotic patient using a balloon

catheter for the first time (4).

Early occlusion of the shunt within a short period due to unsupported parenchymal

shunt was a problem initially. Patency of the shunt improved with the placement of

the stent in the shunt.

In 1988 in Freiburg, first TIPS was performed by using metallic Palmaz stent (5).

With the introduction of USG guidance for visualisation of the portal vein there was

significant reduction in the time taken for the procedure and complications (5).

In 1990 about 50 patients and from 1990 to 1995 about 500 patients were treated

using the same technique (5).

In the past 29 years due to better definition of indications, better patient selection and

improvement in the techniques have resulted in improved clinical outcome (1).

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Current status:

Currently TIPS is a well established procedure usually done by interventional

radiologist. It is used worldwide for treating and managing complications related to

portal hypertension (7). It is usually performed as an elective procedure, however in

the setting of acute variceal bleed it is also performed on an emergency basis within

24 hours of acute variceal bleed not controlled by 2 endoscopic therapies (8).

In the early years due to use of bare metal stents, incidence of shunt dysfunction and

shunt occlusion was much higher which resulted in higher frequency of shunt

revisions. Once the PTFE covered stent was introduced shunt patency rate

significantly improved by reducing the number of shunt revisions. This also improved

the clinical outcome of the patients by increasing the symptom free time period (6).

Amongst the various covered stents used Gore-Viatorr endoprosthesis is the most

commonly used stent.

With technical improvement in the skills and stents there is increase in the shunt

patency and reduction in the complications. In patients with Budd Chiari syndrome

not responding to medical therapy TIPS is considered as treatment of choice. By

offering increased symptom free period it has reduced the need for liver transplant (5).

INDICATIONS:

Portal hypertension is the main complication of cirrhosis of liver. In normal

individuals pressure difference in portal vein and hepatic vein or right atrium is upto

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5mm Hg. Portal pressure gradient more than 6mm is defined as portal hypertension.

Whenever this gradient crosses 10-12mm Hg mark clinical signs start to develop (9).

To reduce this portal pressure multiple collaterals develop as a compensatory

mechanism and cause variceal bleeding. Raised portal pressure also results in

development of ascites and hepatorenal syndrome (10).

Indications for TIPS procedure are listed below:

1) Variceal bleeding:

TIPS is most commonly performed for the treatment of refractory variceal bleeding.

TIPS is useful both for controlling and preventing variceal bleed. In the setting of

acute variceal bleeding, if the bleed is not controlled after 2 sets of endoscopic

therapies within 24 hours TIPS can be placed. TIPS is also useful in case of refractory

esophageal variceal bleeding unresponsive to medical treatment and endoscopic

sclerotherapy or ligation. It is not recommended as first line treatment for variceal

bleed but is reserved in cases of refractory variceal bleed (11).

Various meta-analysis published in the last decade suggested three times decrease in

the rate of recurrent variceal bleeding after TIPS placement in comparision to

endoscopic therapies (12).

2) Refractory ascites:

Refractory ascites is recurrence of ascites inspite of sodium restriction and diuretic

therapy. If untreated patient can develop many complications like spontaneous

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bacterial peritonitis, hepatorenal syndrome and hydrothorax. Large volume

paracentesis (LVP) is a first line treatment for refractory ascites. Many studies have

shown that TIPS is a better treatment option compared to LVP for control of

refractory ascites.

Portal hypertension results due to obstruction to the splanchnic blood flow, this

obstruction causes circulatory disturbances and increased portal, renal and splanchnic

resistance. Placement of TIPS relieves the obstruction with redistribution of

circulatory heamodyamics causing decrease in the renal resistance and in turn

improving renal function.

Thus TIPS has an added advantage of improving the renal function in addition to

control of ascites. Though LVP is a simpler procedure to perform and gives immediate

relief cannot be used for long term management of refractory ascites due to its

negative impact on renal function (5).

Various randomised controlled studies have shown inconsistent results in terms of

survival. Some of the studies do not show any improvement in post TIPS survival

rate, whereas some have shown better survival in patients with TIPS placement (5).

3) Hepatorenal syndrome:

As mentioned above TIPS improves the renal blood flow and in turn improves the

renal function. Hence TIPS has a role in patients suffering from hepatorenal syndrome

(5).

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4) Hepatic hydrothorax:

Development of large pleural effusion in cirrhotics in absence of cardiac or pulmonary

cause is termed as hepatic hydrothorax (12). Ascitic fluid tracks through

diaphragmatic defects in to the pleural cavity (5).

When compared to other treatments, TIPS offers better control over the hepatic

hydrothorax and also prolongs the survival (5).

5) Budd- Chiari syndrome:

Budd Chiari syndrome results due to obstruction of the hepatic vein or IVC occlusion.

This results in portal hypertension. TIPS has a role in treatment of Budd Chiari when

medical treatment fails and hepatic veins are damaged so that angioplasty and stenting

of the vein is not possible. (13). As hepatic veins are damaged direct communication

is created between IVC and portal vein which is called as DIPS (5). It was first

performed in 2001(7).

Placement of TIPS relieves hepatic blood flow obstruction, improves arterial

perfusion there by improving hepatocyte function (13)

6) Extrahepatic portal venous obstruction (EHPVO):

TIPS can be alternative option for management of variceal bleeding related to

EHPVO. It is less invasive compared to surgery and is a valuable treatment in case of

failure of surgery and endoscopic treatment(14).

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Contraindications:

There are many contraindications for TIPS procedure.

Absolute and relative contraindications are listed in table (1) shown below (15)

Absolute contraindications

Relative contraindications

1. Heart failure

2. Severe pulmonary hypertension

3. Severe tricuspid regurgitation

4. Multiple liver cysts

5. Sepsis

6. Unresolved biliary obstruction

7. Central hepatoma

8. Severe coagulopathy

9. Thrombocytopenia (less than

20,000)

10. Moderate pulmonary hypertension

11.Hepatic artery or celiac artery

stenosis

Complications:

Technical complications like capsule perforation, peritoneal haemorrhage and

hemobilia were more frequent in the beginning. With the use of ultrasound guidance

for puncture of the liver and portal vein these complications are almost not

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encountered these days. Other complications like maldeployement, misplacement and

migration of the stent are also very rare these days due to use of Gore-Viatorrstent (5).

Shunt dysfunction, hepatic encephalopathy and liver failure are the major

complications of TIPS procedure (5).

1) Hepatic encephalopathy (HE):

TIPS placement results in diversion of blood flow to the systemic circulation and

reduced liver perfusion (9). Increase delivery of nitrogen substances to brain increases

the risk of hepatic encephalopathy (7).Worsening of pre-existing HE is also noted

(10). Deranged liver function specifically raised bilirubin, advanced age and pre-

existing HE are associated with increased risk of HE (5).

Using left branch of portal vein instead of right branch can reduce the risk of HE (16).

Under dilating or reducing the size of the stents only up to 8mm rather than 10mm

also reduces the risk of HE by reducing the shunt volume (5).

Patients developing hepatic encephalopathy are managed with medical treatment.

Very few patients who develop severe HE and do not respond to medical treatment are

indications for shunt diameter reduction or TIPS occlusion. Shunt reduction can be

achieved by deploying hour glass stent within the previously placed stent (17).

2) Hepatic failure:

It is characterised by rapid derangement of liver function post TIPS placement.

Reduction of liver perfusion post TIPS results in worsening of liver function (17). It

carries poor prognosis and high mortality rate if not treated (5).

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3) Endotipsitis:

It is a rare complication of TIPS and should be suspected in patients with persistent

and unexplained bacteraemia. Treatment options include antibiotics for rest of life or

liver transplant (17).

4) Hernia incarceration:

Placement of TIPS resolves massive ascites leading to alteration in the configuration

of bowel and peritoneal anatomy. This leads to entrapment of bowel, ischemia and

necrosis leading to need for surgery (17).

5) TIPS occlusion:

Early occlusion:

It is common with bare metal stents and occurs due to leakage of bile secondary to

formation of biliary venous fistula. Bile is thrombogenic which predisposes to

thrombus formation and results is acute occlusion of the stent. Hypercoagulable state

is a predisposing factor for early occlusion of the stent and patients with repeated

occlusions should undergo investigations to rule out the same (17). Occlusion results

in recurrence of symptoms, bowel ischemia can occur due to extension of thrombus in

mesenteric veins warranting treatment (18). Acute occlusion is treated with

mechanical thrombectomy or catheter guided instent local thrombolysis followed by

angioplasty (17). Urokinase and heparin are effective for local thrombolysis (19).

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With the wide spread use of Gore-Viatorr endo-prosthesis acute occlusion of the stent

is uncommon. As this prosthesis is covered it prevents the biliary-venous fistula

formation and instent biliary leakage (17).

Gore-Viatorr prosthesis more commonly gets thrombosed due to obstruction to the

blood flow secondary to the structural causes. Structural obstruction occurs following

suboptimal positioning of the stent or migration of the stent (16).

While performing the TIPS procedure during removal of guidewire/catheter can cause

alteration of the stent configuration resulting obstruction to the flow.

Pseudointimal hyperplasia is another reason for shunt dysfunction which causes shunt

stenosis (18).Pseudoitimal hyperplasia results due to aggregation of platelets,

inflammatory cells, RBCs, myofibroblasts and fibrin which form a layer of

granulation tissue. Prior thrombosis and biliary leakage both act as triggering factor

for overgrowth of pseudointima (20).

Pseudointimal hyperplasia can cause simple or complex stent stenosis. Simple stenosis

results due to focal narrowing of the stent secondary to intimal proliferation leading to

web formation. Area of focal narrowing shows increased velocity hence is easy to

detect simple stenosis on USG and Doppler examination.

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Complex stenosis results due to variable thickness of the pseudointima lining the

stent. In this case Doppler of the stent is not reliable and needs evaluation of portal

vein velocity. Reduction of portal vein velocity ranging between 10-20cm/sec

suggests stent dysfunction in this setting (5).

Figure 2a: Simple stenosis: velocities reliable

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As intimal hyperplasia results due to continuing platelet aggregation, platelet

aggregation inhibitors and platelet derived growth factor inhibitors can be useful (19).

6) Radiation dose related complications:

TIPS procedure can be prolonged resulting in increased radiation dose exposure to the

patient as well as the intervention radiologist. Deterministic effects like skin erthema,

ulceration can result (21).

Figure 2b: Complex stenosis: velocities are unreliable

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Various types of stents:

In the beginning bare metal stents were used which included Palmaz stent, Wall stent

and Strecker stents. Examples of covered stents are Gore-Viatorr, ( W.L. Gore,

Flagstaff, AZ)., Fluency covered stent [ Bard] and Niti-S stent (Niti-S stent;

Taewoong, Seoul, Korea) (22). Multiple studies have been performed to analyze

various materials used for covering the stent. Amongst them polytetrafluoroethylene

(PTFE) has given best results (7). Long term shunt patency was significantly

improved following introduction of covered stent (23).

Amongst the various covered stents used, Gore Viatorr stent is most commonly used

stent.

Various stents used in Department of Radiology, CMC Vellore are

-Gore Viatorr stent

-Uncovered stent

-Covered-Uncovered stents combination

- Niti-S TIPS stent

Gore Viatorr stent:

It was introduced in 1999, after European multicenter trial, available since 2001, FDA

approval in December 2004 (24).

In India it is available since 2005.

Structural support is provided by an external self-expanding nitinol stent (25).

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Intrahepatic portion of the stent is covered with PTFE whereas the bare part lies in the

portal vein (8).

Covered and uncovered portion, interface is demarcated by radio-opaque gold ring

(25). This demarcation is useful for positioning of the stent during the procedure (26).

Additional radiopaque gold marker is at the proximal end which helps fluoroscopic

visualisation during deployment (8).

Covered portion has 3 layers of PTFE with varying pore diameters which completely

blocks the instent biliary leakage. It also prevents growth of liver tissue within the

stent and covers part of the hepatic vein neat the puncture site. All these factors help

in preventing thrombosis of stent (27).

Fluency stent:

It also is covered by PTFE but has 2 layers instead of 3 layers.

Covering is not same as VG, uses carbon along the inner layer which prevents platelet

aggregation (23).

Angermayr et all have retrospectively demonstrated an improved survival rate of 88%

at 1 year for patients treated with the VIATORR1endoprosthesis for TIPS, compared

with 73% for a matched group receiving bare stents. Survival rate after TIPS creation

with the VIATORR device is higher than that after TIPS creation with an uncovered

stent (8).

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Niti-S TIPS stent:

This stent has been used exclusively in our department since 2015 onwards as Gore

Viatorr is not available in India.

Niti-S TIPS stent is being used since 2015 onwards as Gore Viatorr is not available in

India. English literature available about Niti-S TIPS stent patency and clinical

outcome are sparse and furthermore no Indian study is available.

It is a mesh-type stent interlaced with a nitinol monofilament (25).

Nitinol monofilament wire is wound on a mandrel to create a spiral mesh at

deployment, the stent self-expands to a predetermined diameter of 8–10 mm with a

length of 6–10 cm (20).

It has constant 20mm uncovered portion and variable covered portion [varying from

40mm to 100mm (20).

Technique of TIPS procedure:

It can be performed using sedation or under general anaesthesia. After puncturing the

right internal jugular vein, IVC is accessed and catheter venogram is taken and

pressures in the right atrium and IVC is measured. Right branch of portal vein is

punctured and portogram is done, pressure in the portal vein is measured. Intrahepatic

parenchymal track is dilated using balloon catheter. Stent is deployed within this intra-

parenchymal track after which post TIPS pressures are measured.

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Variations in the TIPS procedure technique:

Intravascular ultrasound can be used to guide the puncture while performing TIPS

(25).

In the setting of jugular vein thrombosis femoral vein can be used for access (7).

In case of occluded portal vein, portal vein can be accessed through percutaneous

approach which is combined with Transjugular approach. Percutaneous approach

allows easy access to the portal vein which can be then recanalised. Balloon is inflated

within this recanalised portal vein. Using the Transjugular approach needle is targeted

to the inflated balloon in the portal vein. Once the balloon is punctured it assures that

the needle is in the portal vein (7).

Monitoring TIPS patients:

Monitoring of TIPS patients need follow up at regular intervals, usually it is done at

1st week, at 3 months, at 6 months and yearly thereafter if no symptoms develop. If

there is worsening of symptoms or development of new symptoms patient is advised

to follow up immediately (28).

Regular follow up involves clinical assessment, Doppler evaluation and laboratory

parameter evaluation. Clinical evaluation involves assessment of decrease in the

symptoms, worsening of symptoms or development of new symptoms.

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Doppler is an important investigation to check the shunt patency. Before interpreting

the Doppler findings it is important to be aware of the normal anatomy and normal

flow pattern of the shunt.

Shunt has 3 parts, caval end of shunt is called as cephalic part, portal end is called as

caudal end with intervening segment is called as mid stent.

As this shunt is a low resistance pathway blood from the portal end flows towards the

caval end, hence normal direction of flow within the stent is hepatofugal.

Figure 3a: normal flow pattern in shunt

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Figure 3b showing flow pattern in shunt

Figure 3c showing flow pattern in shunt

Shunt can show complete/ partial thrombosis or stenosis in a particular region. In case

of complete thrombosis there will be complete absence of colour flow in the stent.

Cephalic flow Caudal flow

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Stenosed segment will show high velocities within. Shunt velocities are usually taken

at portal end, mid part of the stent and caval end of the stent. Velocities more than

180cm/sec and less than 90 cm/sec are considered abnormal or change in velocity by

50cm/sec is also considered abnormal. Main portal vein velocity more than 30 cm/sec

is considered normal. Post TIPS patients show hepatofugal flow. Change in the

hepatofugal flow to hepatopetal flow is considered abnormal. Presence of new or

increased collateral vessel also suggests TIPS dysfunction (29).

Cirrhotic patients are also checked for development of any focal lesions in the liver if

so these lesions need further evaluation to rule out hepatocellular carcinoma.

Along with this patients also undergo laboratory parameter evaluation which includes

Role of other imaging modalities:

Catheter venogram and Contrast enhanced CT abdomen are other imaging modalities

that can be used to asses shunt patency.

Patient with suspected shunt malfunction based on symptoms and Doppler findings

undergoes catheter venogram. Absence of filling of shunt on catheter venogram

suggests shunt block, with narrowing of the shunt lumen with high pressure gradient

across port-systemic circulation suggests stensosis.

If the catheter venogram shows stenosis balloon angioplasty of the stent is done. In

case of complete occlusion thrombolysis and thrombectomy is done.

On contrast enhanced CT abdomen, complete occlusion is seen as non-opacification

of the shunt where as partial opacification suggests partial thrombosis.

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Success of TIPS procedure:

Technical success: It is defined as correct creation of an intra-hepatic channel

between IVC/hepatic vein and portal vein. It also includes proper placement of the

stent within this channel (7).

Heamodynamic success: Heamodynamic success means decrease in the porto-

systemic gradient to 12mm Hg or below it. It can also be defined as reduction of this

gradient by 20% (9).

Clinical success:It is measured in terms of improvement in the clinical signs and

symptoms of the patient and patency of the stent over a period of time (7).

Technical

success

Clinical success

Heamodynamic

success

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Treatment of TIPS stenosis and TIPS occlusion:

Patients having shunt occlusion are treated with thrombectomy, thrombolysis and

balloon angioplasty.

Patients with TIPS stenosis are treated with balloon angioplasty.

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MATERIALS AND METHODS:

Study period:

The study was conducted in the Department of Radiology in the period between July

2016 to August 2017 after obtaining approval from the Institutional Review Board

(IRB Min No 9963 dated 02/03/2016)

In this study comparison of clinical outcome and primary and secondary

patency of Gore-Viatorr and Niti-S stents was conducted. All the patients who

had already undergone TIPS in Department of Radiology and patients

undergoing TIPS during August 2016 to July 2017 were included in this study.

Data from the year of 1999 was collected and retrospectively analyzed, whereas

data collected from patients undergoing TIPS during August 2016 to July 2017 was

prospectively analyzed.

Study design: prospective and retrospective cross sectional descriptive study

Recruitment of subjects:

Inclusion criteria:

All the patients who have undergone TIPS procedure in the Department of

Radiology, CMC Vellore from 1999 onwards were included in the study

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Patients who needed TIPS or DIPS and underwent stent placement during August

2016 to July 2017 were prospectively analysed. In all these patients Niti-S stent was

used as Gore Viatorr was not available in India, informed consent was taken by the

principal investigator.

Patients who underwent additional placement of stent along with primary stent as

Niti-S or Gore Viatorr stents were also included in the study. Additional stent placed

was Fluency stent in 3 patients.

Exclusion criteria:

Patients with severe heart failure, severe pulmonary hypertension and severe

encephalopathy were excluded and did not undergo the procedure.

Patients who underwent TIPS or DIPS with primary stent other than Niti-S and Gore

Viatorr stents were excluded.

Sample size calculation:

The required sample size to compare the primary patency rates across Gore Viatorr

and Niti-S stents used in Transjugular intrahepatic portosystemic shunt

(TIPS) was found to be 49 in each of the groups with 80% power and 5% level of

significance when the expected difference in the patency rates was considered as

30%.

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Formulae and tables for the determination of sample size and power in clinical trials

for testing differences in proportions for the two sample design: a review.

Statistics in Medicine, 1996; 15: 1-21.

Proportion in group (primary patency rate in

Gore Viatorr0.77 0.77 0.7 0.7 0.7 0.7

Proportion in group (primary patency rate

in Niti S stents) 0.66 0.5 0.6 0.55 0.5 0.45

Estimated risk difference 0.11 0.27 0.1 0.15 0.2 0.25

Power (1- beta) % 80 80 80 80 80 80

Alpha error (%) 5 5 5 5 5 5

1 or 2 sided 2 2 2 2 2 2

Required sample size for each arm 263 49 35 6 93 60

Formula:

Where, P1 = 77%

P2 = 50%;

Power = 80%; Level of significance = 5%

Reference for the above formula: Sahai H, Kurshid A.

Two Proportion - Hypothesis Testing - Large Proportion - Equal Allocation

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Data collection:

All the demographic details of the patients along with indication for TIPS procedure,

cause of portal hypertension and cirrhosis of liver, type, number and dimensions of

stent used, presence of hypercoagulable state, post TIPS symptoms, Doppler findings,

catheter venogram findings and treatment of shunt failure were collected using a

questionnaire.

All the patients who had already undergone TIPS procedure all the above mentioned

data was collected from the clinical work station and PACS system.

Those who underwent TIPS procedure during July 2016 to August 2017 time period

informed written consent of the patient was taken before the procedure and above

mentioned data was collected

TIPS Procedure:

Pre-intervention measures:

Patients having large volume ascites or hydrothorax underwent tapping. This helped in

positioning the liver in a more favourable position for portal puncture. It also

improved DSA image quality and reduced radiation exposure. Also improved

respiratory function and helped during sedation.

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Pre TIPS Imaging:

Ultrasound and Doppler examination was done to rule out portal vein thrombosis,

portal cavernoma formation, hepatic vein thrombosis, hepatic arterial pathologies and

liver cyst or tumour, collaterals, splenic size and ascites.

Assessment of vascular anatomy and most suitable hepatic vein was selected for the

procedure, if the hepatic veins were damaged and not accessible DIPS was planned.

Laboratory tests were doneto evaluate renal and liver function, MELD score, Child

Pugh classification, prothrombin time, partial thromboplastin time, INR, complete

blood count, cardiac evaluation was done to rule out existing cardiac disease.

Hepatic encephalopathy was ruled out, those patients who had hepatic encephalopathy

were medically managed.

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Setting and location:

TIPS procedure was performed in DSA suite situated on the ground floor of main

block of CMC hospital.

DSA Suite in Department of Radiology

Seimens artis zee, biplane machine

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Doppler examinations were performed using Toshiba machines in room 8C, 9A, 9B

and Asha Doppler room 11 in Department of Radiology, Christian medical Hospital,

Vellore.

Toshiba machine in room 8C

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Equipments:

18G puncture needle

Vascular sheaths 9F, 10F

0.035 inch J guide wire

TJLB cannula

Rosch Uschida needle

Pigtail catheter, maker pigtail catheter

Balloon catheters

Nitis-S stent

Rosch-Uchida Transjugualr Liver access Set (Cook medical)

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Niti-S stent used in our study

Technique of TIPS:

Procedure was performed in DSA suite.

It was performed using sedation or under general anaesthesia.

Using ultrasound guidance right internal jugular vein was punctured using 18G

needle.

IJV access was secured with 9F sheath and then upgraded to 10F sheath.

5000 IU Heparin bolus was given during the procedure.

J guide wire (0-.035 inch) was introduced through this sheath and advanced in to the

itra-hepatic IVC under fluoroscopic guidance and venography was performed using

Pigtail cathter, pressure in the right atrium and IVC is measured.

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TJLB cannula was introduced in to the IVC through which Rosch uchida needle was

advanced in to the cannula.

Under USG guidance right hepatic vein or IVC was punctured, needle was advanced

in the hepatic parenchyma and then right branch of the portal vein was punctured,

marker Pigtial catheter was passed over the guide wire, venography was performed

and pressure in the portal vein was measured.

Amplatz wire was passed through the marker pigtail catheter, intra-parenchymal track

was dilated using balloon catheter.

Length of the required stent was measured depending upon the number of markers

present over the pigtail catheter in the parenchyma. Expandable covered metallic stent

was deployed within the tract, covered portion lies within the hepatic parenchyma,

uncovered part of the stent which measured 2cm lies within the portal vein, this

uncovered portion allows free flow of blood through interstices and prevents thrombus

formation.

Balloon dilatation of the stent was done upto desirable diameter usually upto 10mm,

in case of patients with hepatic encephalopathy stent is dilated upto 8mm to reduce the

shunt volume

Last step was post TIPS check portogram and post TIPS pressure measurements in the

portal vein and the right atrium using pigtail catheter.

47

Variations in procedure:

1) One patient already had IVC stent, in this patient TIPS stent was placed through

the struts of the IVC stent, this is called as strutpalsty.

2) Many of the patients had two stent placements when length of one stent was not

enough.

3) When right branch of portal vein was difficult to access left branch of portal vein

was used.

4) Few of the patients having shunt malfunction underwent stent within stent

placement when adequate recanalisation was not possible with thrombolysis,

thrombectomy and balloon angioplasty

Figure 4a : showing IVC catheter

venogram

Figure 4b : showing portogram

IVC

sh

ow

ing

por

tog

ra

m

Pigtail

catheter

gram

Pigtail

catheter

showin

g

portogr

am

Portal vein

48

Figure 4c: showing dilatation of

parenchymal tract using balloon

catheter

Figure 4d: showing marker pigtail

insertion

Figure 4e: showing dilatation of the

deployed stent

Figure 4f: showing opacification of

the stent

Balloon

catheter

Marker

pigtail

catheter

Stent graft

Balloon

within

the stent Stent graft

49

Post TIPS follow up:

Regular follow up of these patients was done within 1week, at 1, 3, 6 months, at 1st

year, every 6 monthly after 1 year.

Clinical examination and Doppler examination was part of routine evaluation.

a) Clinical outcome:

It was measured in terms of reduction of symptoms, no new symptoms, development

of new symptoms and worsening of symptoms.

Shunt patency was evaluated using Doppler findings and or catheter venogram

findings.

b) Doppler evaluation:

It included, whether the shunt is patent or blocked. Shunt velocities were taken at

portal end, mid shunt and caval end. Velocities within 90-190 cm/sec range were

considered normal. Velocities above below 90 and above 190 were considered

abnormal. Main portal vein velocity above 30 cm/sec was considered normal,

velocities below 30cm/sec were considered abnormal.

Increase or development of new collaterals, new appearance ascites or increase in

ascites was also checked for, and if present was considered abnormal.

c) Catheter venogram:

If the patient was symptomatic and Doppler was abnormal patient underwent catheter

venogram with pressure gradient measurement. If patient was symptomatic and

Doppler was abnormal or if patient was asymptomatic and Doppler was abnormal

patient underwent catheter venogram with pressure gradient measurement.

50

Presence of narrowing of the stent lumen with high pressure gradient was considered

as shunt stenosis. Non opacification of the shunt was considered as shunt occlusion.

d) Shunt revision:

If catheter venogram findings were abnormal patient underwent balloon angioplasty.

Patients with shunt occlusion were treated with thrombectomy, thrombolysis followed

by balloon angioplasty. Those patients who had shunt stenosis underwent balloon

angioplasty alone. Patients who showed persistent shunt narrowing even after balloon

angioplasty had additional stent placement within the previously existing stent. These

patients who had shunt revision were also regularly followed up.

51

SUMMARY OF METHODOLOGY:

Figure 5: showing summary of methodology

Patient

Clinical assessment in OPD

Radiology Department: Doppler /CT

Follow up: Post procedure follow up to 1 week; 1, 3, 6 months 1st

year, every 6 monthly after 1 year

Asymptomatic and

normal Doppler

Symptomatic and

abnormal Doppler

Symptomatic and

normal Doppler

Asymptomatic and

abnormal Doppler

Follow up Follow up Catheter

venogram

Normal Abnormal

Follow up Balloon angioplasty

Follow up

TIPS Procedure

52

Statistical analysis:

Data entry was performed using Epidata Entry version 3.1, a dedicated data entry

software. Statistical analysis was performed using SPSS version 20.0 software. A p

value of less than 0.05 indicated statistical significance.

Discrete variables are reported as proportions.

Continuous variables are reported as Mean ± SD or median and interquartile range.

Primary patency rate and secondary patency rate was calculated using Kaplan Meier

survival analysis.

Statistical significant association between two groups were calculated using Log rank

test and Pearson’s correlation test was used to analyze the correlation between

primary patency rate of Gore-Viatorr and Niti-S stents

53

RESULTS

Patient characteristics:

1. Age distribution

2. Gender distribution:

Amongst total number of patients 53 were males and 28 were females

Figure 6: showing gender distribution among patients

65%

35%

Total 81

Males - 53 Females - 28

Age distribution: Mean age of patients was 37.8, range was from 13 to 76 years

54

Gender distribution among patients with Gore-Viatorr and Niti-S is shown by

column chart below

Figure 7: showing gender distribution among two groups

Amongst total 45 Gore Viatorr 25 were males, 20 were females

Amongst total 36 Niti-S patients 24 were males, 8 were females

3. Type of stent used

Out of total 81 patients, 45 patients had Gore-Viatorr and 36 patients has Niti-S

stent placement.

25 24

20

8

Gore Viatorr Niti-S

Males Females

55

Figure 8: showing distribution of patients among each type of stent

4. Indication for TIPS/DIPS:

Most common indication for TIPS/DIPS in our study was refractory ascites.

Out of total 81 patients 60 had an indication of refractory ascites contributing

to 79% of cases. Second most common cause was variceal bleeding. 12 patients

had an indication of variceal bleeding which accounted for 15% of cases.

Bridge to liver transplant was an indication among 3 patients accounting to 3.7

% of cases. Least common indication was refractory hydrothorax. Only 2

patients had this indication which accounted for 2.5% of cases.

Viator Gorre

- 45

55%

Niti-S - 36

45%

Total 81stents

56

Indication for TIPS

Number of patients

Refractory ascites

60 (79%)

Variceal bleeding

12 (15%)

Refractory hydrothorax

2 (3%)

Bridge to liver transplant

3 (4%)

Table 2: showing distribution of indication for TIPS in all patients

Figure 9: showing percentage distribution of indications for TIPS procedure

Refractory ascitis

-79%

Variceal bleeding

-14.8%

15%

Refractory

hdrothorax -2.5%

3%

Bridge to liver

transplant -3.7%

4%

57

Most common indication for TIPS in Gore Viatorr group was refractory ascites. Out

of total 45 patients of Gore Viatorr 37 patients had TIPS due to refractory ascites.

Second most common cause was variceal bleeding, 7 patients had this indication. Out

of remaining 2 patients 1 patient had TIPS due to refractory hydrothorax and other 1

had as to bridge to liver transplant.

Most common indication for TIPS in Niti-S was also refractory ascites. Out of total 36

patients of Niti-S 24 patients had TIPS due to refractory ascites. Second most

common cause was variceal bleeding, 5 patients had this indication. Out of remaining

3 patients 1 patient had TIPS due to refractory hydrothorax and other 2 had as a bridge

to liver transplant.

Indication

Gore Viatorr (45)

Niti-S (36)

Refractory ascites

36

24

Variceal bleeding

7

5

Refractory hydrothorax

1

1

Bridge to liver transplant

1

2

Table 2: showing indication for TIPS in patients with Gore Viatorr and Niti-S

58

5) Cause of portal hypertension:

In our study most common cause of portal hypertension was Budd Chiari syndrome.

Out of total 81 patients 56 had Budd Chiari. Second most common cause of portal

hypertension was alcoholic liver disease. 10 patients had alcoholic liver disease. 5 had

cryptogenic cirrhosis, 4 had HBV/HCV related liver disease, 3 had NAFLD (non

alcoholic fatty liver disease). Non cirrhotic portal hypertension, Wilson’s disease

veno-occlusive disease had 1 patient each.

0

5

10

15

20

25

30

35

40

Viatorr Gore Niti-S

Refractory ascitis

Variceal bleeding

Refractory

hydrothorax

Bridge to liver

transplant

Figure 10: showing indication of TIPS procedure in Gore Viatorr and Niti-S

stent

59

Figure 11: showing distribution of causes of portal hypertension

Cause of portal hypertension

Total number of

patients

Budd Chiari syndrome

56 (69%)

Alcoholic liver disease

10 (13%)

HBV/HCV infection

4 (5%)

Cryptogenic cirrhosis

5 (6%)

NAFLD

3 (4%)

Non cirrhotic portal

hypertension

1 (1%)

Wilsons disease

1 (1%)

Veno-occlusive disease

1 (1%)

Table 3: showing distribution of causes of portal hypertension

69%

13%

6% 5%

4% 1% 1% 1%

Budd Chiari Alcoholic liver disease

Cryptogenic HBV/HCV

NAFLD Non cirrhotic portal hypertension

Wilsons disease Veno-occlusive disease

60

Cause of portal

hypertension

Gore

Viatorr(45)

Niti-S (36)

Budd Chiari syndrome

33 (73%)

23 (63.8%)

Alcoholic liver disease

3 (6.6%)

7 (19%)

HBV/HCV infection

1 (2%)

3 (8%)

Cryptogenic cirrhosis

3 (6%)

2 (5%)

NAFLD

2 (4%)

1 (2%)


hypertension

1 (2%)

0 (0%)

Wilsons disease

1 (2%)

0 (0%)


1 (2%)

0 (0%)

Table 3: showing cause of portal hypertension in patients with Gore Viatorr and

Niti-S stent.

Most common cause of portal hypertension in Gore Viatorr group of patients was

Budd Chiari syndrome. 33 out of 45 patients had Budd Chiari syndrome accounting

for 73% of cases. Second most common causes of portal hypertension were

cryptogenic cirrhosis and alcoholic liver disease having 3 patients each accounting for

6.6% of cases. Remaining causes were NAFLD (non alcoholic fatty liver disease)

accounting for 2 cases and other causes like HBV/HCV related liver disease, non-

cirrhotic portal hypertension and veno-occlusive disease had 1 patient each.

61

Most common cause of portal hypertension in Niti-S group of patients was Budd

Chiari syndrome. 23 out of 36 patients had Budd Chiari syndrome. Second most

common causes was alcoholic liver disease accounting for 7patients. Cryptogenic

cirrhosis had 2 patients and NAFLD (non alcoholic fatty liver disease) had 1 patient.

Figure 12: showing distribution of causes of portal hypertension among two

groups

6) Stent dimensions:

In our study mean length of the stent was 8.9 cm (+/-2 cm), minimum length of the

stent was 4cm and maximum length was 12cm.

0 10 20 30 40

Viatorr

Gore

Niti-S


Wilson's disease


hypertension

NAFLD

Cryptogenic

HBV/HCV

Alcohol 2

Budd Chiari

62

Amongst the Gore Viatorr mean length of the stent was 8.2 cm(+/-2 cm),

minimum length of the stent was 4cm and maximum length was 10cm.

Amongst the Niti-S patients mean length of the stent was 9.7 cm(+/-2 cm),

minimum length of the stent was 6cm and maximum length was 12cm.

All the stents had a diameter of 10mm.

7) Outcome:

Outcome was measured in terms of technical success, heamodynamic success and

clinical success.

Technical success:

Technical success was defined as correct creation of a shunt with successful

placement of stent within the channel.

All the patients had a successful TIPS procedure with technical success rate of 100%.

Hemodynamic success:

Heamodyamic success was defined as decrease in the porto-systemic gradient to

12mm Hg or below or reduction of this gradient by 20% and was achieved in 100% of

cases.

Mean pre TIPS pressure gradient was 21.6 +/- 0.6 mm of Hg

Mean post TIPS pressure gradient was 8.4 +/- 0.4 mm of Hg

Mean reduction in the pressure gradient 13. 2 +/- 2 mm of Hg

63

Clinical success:

It was defined as improvement in the clinical signs and symptoms of the patient and

patency of the stent over a period of time.

Patency of shunt was determined in terms of Doppler findings, catheter venogram

findings, shunt blockage and number of shunt revisions required.

Clinical findings:

Out of total 81 patients, 18 had development of new symptoms or worsening of

symptoms at varying time interval, 9 belonged to Gore Viatorr and 9 belonged to Niti-

S group, remaining 43 patients showed improvement in the clinical symptoms over a

varying time period of 1 month to 11 years, 20 patients were lost to follow up after 1

week of post TIPS. Out of the total 18 patients who had symptoms 7 developed

recurrence of symptoms after first revision of the stent, remaining 11 patients

remained asymptomatic during their follow up.

Out of the 18 patients, 16 had refractory ascites and 2 had variceal bleeding. All the 9

patients in Gorre Viatorr group had refractory ascites which showed development of

ascites after a symptom free period varying from 3 months to 4.3 years.

In the Niti-S group, 7 patients had refractory ascites and 2 had variceal bleeding. Out

of the 7 patients 4 died within 30 days post TIPS, 1 had development of ascites after

symptom free time of 7 months and recurrence of symptoms at varying intervals

needing atleast 6 shunt revisions, he was not evaluated for hypercoagulable state.

Remaining 2 patients were followed up for 1 year and do not have any symptoms

64

during this time period. One patient with variceal bleeding had pain in abdomen on

day 5 of TIPS, imaging showed shunt occlusion was treated for same. Other patient

with variceal bleeding developed abdominal distension 7 month post TIPS, in this

time period he had no episode of variceal bleed, on evaluation he was found have

hypercoagulable state.

Out of 18 patients with shunt malfunction 16 had Budd Chiari syndrome, 1 had

alcoholic liver disease and 1 had cryptogenic fibrosis as a cause of portal

hypertension. Out of the 9 Gore Viatorr patients, 8 had Budd Chiari syndrome and 1

had cryptogenic cirrhosis. Out of 9 Niti-S group of patients 6 had Budd Chiari

syndrome and 2 had alcoholic liver disease as a cause of portal hypertension.

Out of the 18 patients with shunt malfunction 4 had hypercoagulable state and all

these 4 patients had Budd Chiari as a cause of portal hypertension, rest 14 patients

were not evaluated for underlying hypercoagulable state. Out of these 4, Gore Viatorr

had 2 and Niti-S group had 2 patients each. One of the Gore Viatorr group patient had

multiple shunt blocks and needed 3 revisions, remaining one patient was lost to follow

up after 1 week of TIPS revision. Both patients in Niti-S group were symptom free

for 1 year and 2 years respectively post TIPS revision.

Doppler findings:

Out of the total 81 patients 18 had shunt malfunction, 11 had shunt occlusion and

remaining 8 had shunt stenosis according to the Doppler criteria defined in our study.

65

Figure 13: showing distribution of patients in causes of shunt failure

Stent type

Shunt occlusion

Shunt stenosis

Gore Viatorr

4

5

Niti-S

7

2

Table 4: showing distribution of causes of shunt failure among each group

Shunt occlusion-

11 61%

Shunt stenosis- 7

39%

Shunt malfunction-Total 18

66

Figure 14: showing distribution of causes of shunt failure among each group

Total 7 patients who had shunt stenosis 5 belonged to Gore Viatorr group and 2

belonged to Niti-S group.

Amongst the Gore Viatorr group of patients 3 patients had abnormally high shunt

velocity, 1 patient had abnormally low shunt velocity and 1 patient did not have

documentation of velocities before catheter venogram. Abnormally high shunt

velocities were seen at portal end and at caval end. 2 patients had high shunt velocities

at portal end and 1 had at caval end. Two patients had shunt velocities more than 210

cm/sec and 1 had velocity more than 184cm/sec. All these patients had these high

velocities on two follow ups during 6 month, 1 year and 2 years respectively. On the

third follow when they developed symptoms, they underwent catheter venogram,

findings were confirmed on catheter venogram and patients underwent balloon

0

1

2

3

4

5

6

7

8

Gore Viatorr Niti-S

Shunt occlusion

Shunt stenosis

67

angioplasty. Patient with low velocity had showed low velocities at all the 3 parts of

the shunt and were below 80 cm/sec at 1 year but was asymptomatic, on follow at 2

years post TIPS his velocities remained persistently low but at this time he had

developed new symptoms. This patient underwent catheter venogram, showed

narrowing at caval end and underwent shunt revision.

Of the total 11 patients who had shunt occlusion 4 belonged Gore Viatorr group and 7

belonged to Niti-S group. These patients showed absence of colour flow and absence

of on spectral waveform on Doppler examination. Amongst the Gore Viatorr group,

patients developed shunt occlusion between 1 year to 3 years time period. Among the

Niti-S group 4 out of 7 patients developed shunt occlusion in less than 20 days and

remaining 3 developed over a period of 6 months to 1 year period.

Doppler images of a patient with development of new symptoms in the form of

abdominal distension post TIPS

Figure 15a: showing absence of colour

flow within the stent suggestive of shunt

occlusion

Figure 15b: showing absent spectral

wave from with artifactual flow within

the stent

68

Absence of colour flow within the stent, absent spectral waveform, presence of

significant ascites and development of new splenic hilar collaterals all these findings

are suggestive of shunt occlusion. Following this patient underwent catheter catheter

venogram.

Figure 15c: showing significant ascites Figure15d: showing multiple splenic

hilar collaterals

Catheter venogram

images

Figure 15d: showing non

opacification of the shunt

suggestive of shunt occlusion

Figure 15e: showing opacification

of the shunt post thrombolysis and

BA

69

Catheter catheter venogramconfirmed shunt occlusion, patient underwent

thrombectomy, thrombolysis and balloon angioplasty (BA).After the procedure patient

had regular follow up.

Doppler images of a patient with worsening of symptoms in the form of increasing

abdominal distension post TIPS

Figure 16a: showing focal

narrowing of the mid part of the

stent

Figure 16b: showing abnormally

high velocity (218 cm/sec) within

the narrowed stent segment

70

This patient had catheter catheter venogram which confirmed the findings of the

Doppler.

Figure 16c: showing focal filling

defect in the mid part of the stent

suggestive of stenosis

Figure 16d: showing normal

opacification of the stenosed

segment post balloon angioplasty

71

Shunt patency:

Primary patency rate was defined as duration of stent patency without revision.

Secondary patency rate was defined as duration of stent patency after first revision.

Primary patency rate and secondary patency rate was calculated using Kaplan Meier

survival analysis.

Statistical significant association between two groups were calculated using Log rank

test.

Primary patency rate:

Figure 17: Kaplan Meier curve for primary patency rate

72

Types of Stents

Time (in months)

Gore Viatorr

Niti-S

P value

Primary patency rate %

Standard error

(SE)

Primary patency rate %

Standard error

(SE)

3 months

96.4

0.035

80.8

0.071

6 months

92.7

0.050

70.7

0.113

9 months

88.9

0.061

70.7

0.113

<0.001

12 months

88.9

0.061

50.5

0.145

24 months

76.7

0.084

37.9

0.154

Table 5: showing primary patency rates of Gore Viatorr stent at various

intervals

73

Primary patency rate of Gore Viatorr stent at 3 month, 6 month, 9 month, 1 year and 2

years were 96.4%, 92.7%, 88.9%, 88.9%, 76.7% respectively.

Primary patency rate of Niti-S stent at 3 month, 6 month, 9 month, 1 year and 2 years

were 80.8%, 70.7%, 70.7%, 50.5%, 37.9% respectively.

Mean follow time for Gore Viatorr patients was 7 years +/- 1 year.

Mean follow time for Niti-S patients was 1.1 years +/- 2 months.

Overall Comparisons

Chi-Square

df

Sig.

Log Rank (Mantel-Cox)

12.579

1

.000

Tarone-Ware

12.499

1

.000

Table 6: comparing association between primary patency rates of Gore Viatorr

and Niti-S

Association between two groups was calculated using Log rank method which showed

p value of < 0.001 at all intervals ie at 3 month, 6 month, 9 month, 1 year and 2 years

suggesting the there is significant difference between primary patency rates of Gore-

Viatorr and Niti-S stent at all calculated intervals.

74

Secondary patency rate:

In our study out of total 81 patients 18 patients developed shunt malfunction in the

form of shunt stenosis or shunt blockage.

Out of these 18 patients 9 had Gorre Viatorr and 9 had Niti-S stent placement. Out of

9 patients which underwent first balloon angioplasty, 6 had one or more incidences of

shunt malfunction during the follow up period and needed additional shunt revisions.

Only one out of 8 patients of Niti-S developed 2nd

incidence of shunt malfunction.

This patient needed 6 shunt revisions. 4 patients died within 15 days post TIPS. 3

patients who were followed up for approximately 1 years post TIPS did not have shunt

malfunction during the follow up period.

Mean follow time for Gore Viatorr patients was 8.57 years +/- 8 months.

Mean follow time for Niti-S patients was 1.9 years +/- 3 months.

75

Figure 18: Kaplan Meier curve for secondary

patency rate

76

Table 8: showing secondary patency rates of Gore Viatorr at various intervals

Secondary patency rates of Gore-Viatorr at at 3 month, 6 month, 9 month, 1 year and

2 years were 96.9 %, 92.9%, 89%, 85.8%, 75.9% respectively.

Secondary patency rates of Niti-S stent at 1 year and at 2 years was 75%.

Types of Stent

Time (in

months)

Gore Viatorr

Niti-S

P value

Secondary

patency rate

%

Standard

error

(SE)

Secondary

patency

rate

%

Standard

error

(SE)

0.230

3 96.9 0.032 - -

6 92.9 0.049 - -

9 89.0 0.060 - -

12 85.8 0.077 75 0.02

24 75.9 0.087 75 0.02

77

Overall Comparisons

Chi-Square df Sig.

Log Rank (Mantel-

Cox) .077 1 .781

Tarone-Ware .147 1 .702

Table 9: showing association between secondary

patency rates of both groups

Though the Log rank test did not show any statistical difference between the

secondary patency rates of two stents and p value was more than 0.005.

Thus statistically it suggests that there is no significant difference between the

secondary patency rates of both stents.

Mortality:

In our study total 7 deaths were documented. 5 out of these 7 deaths occurred in less

than 30 days post TIPS. Remaining 2 deaths occurred in 2nd

year and 4th

year post

TIPS respectively.

Amongst these 7 deaths, 3 patients had Gore Viatorr stent placement and 4 had Niti- S

stent placement.

78

Those patients who had Gore Viatorr stent, one death was documented on day 4 post

TIPS. This patient had underwent emergency TIPS for acute variceal bleeding,

developed hypotension during the procedure, on day 2 he had worsening liver

function which was thought to be due to liver infarction, day 4 he developed malena,

during this period shunt was patent on Doppler evaluation, he succumbed to the illness

on day 4 post TIPS. 2 deaths occurred in 2nd

year and 4th

year post TIPS respectively

cause of which is not known as these patients did not follow up in our hospital and

outside documents are not available.

All the 4 deaths in patients with Niti-S occurred in first 30 days post TIPS. One

patient developed intestinal obstruction and one developed gangrene bowel during

post op 1st week for which they were operated, developed sepsis in post op period and

succumbed to the illness. One of the patient developed spontaneous bacterial

peritonitis and acute kidney injury. The other patient developed hypotension during

the procedure, continued to remain unstable post op and died on day 2 post TIPS.

Post TIPS survival rate:

It was defined as time taken for death of the patient after the procedure.

It was calculated using Kaplan Meier curve for both group of patients.

In our study there was no statistical difference between the two groups suggesting

that post TIPS survival rate was similar for both groups.

79

Figure 20: Kaplan Meier curve showing survival rate in Gore Viatorr and Niti-

S groups of patients.

80

Post TIPS survival rate in Gore Viatorr at 3month to 1 year, 2 years and at 3 to 10

years was 97.9%, 92.9%, 82% respectively.

Post TIPS survival rate in Niti-S at 3month to 1 year, 2 years and at 3 to 10 years was

86%.

Types of Stents

Time Gore Viatorr Niti-S

Survival

rate

%

Standard error

(SE)

Survival rate

%

Standard

error

(SE)

3month to 1 year

97.9

0.02

86

0.06

2 year

92.9

0.05

86

0.06

3 to 10 year

82.0

0.07

-

-

Table 10: showing post TIPS survival rates in two groups

81

Overall Comparisons

Chi-Square df Sig.

Log Rank (Mantel-Cox) 2.474 1 .116

Tarone-Ware 2.547 1 .110

Table 11: comparision of post TIPS survival rate among two groups

P value is not less than 0.005, hence there is no significant difference between the post

op survival rate of Gore Viatorr and Niti-S patients.

Liver transplant:

3 patients underwent liver transplant within 1-3 months post TIPS. Out of 3, 1 of them

had Gore Viatorr stent and 2 had Niti-S stent placement.

Additional stent placement:

Total 6 patients had additional stent placement. 3 of them were placed along

with the main stent itself during the TIPS procedure. All these additional stents

placed were Fluency stents and all the patients had Gore Viatorr as the main

stent.

82

3 patients had an additional stent placement within the previous stent as part of

treatment. In these patients when the shunt stenosis was not relieved even after

balloon angioplasty they had additional stent placement within the previously existing

stent. One patient belonged to Gorre Viatorr and other 2 belonged to Niti-S group of

patients.

83

SUMMARY OF RESULTS:

Secondary

patency rate

1 year – 75%

2 years - 75%

3 months –

96.9%

6 months –

92.9%

1 year –

80.8%

2 years –

75.9%

Clinical

Doppler

Catheter venogram

Gore Viatorr -

45

Total patients - 81 Niti-S - 36

Gore Viatorr -

9

Total Shunt

Malfunction - 18 Niti-S - 9

Primary

patency rate

Secondary

patency rate

Primary

patency rate

3 months –

96.4%

6 months –

92.7%

1 year –

88.9%

3 months –

80.8%

6 months –

70.7%

1 year –

50.5%

84

DISCUSSION:

TIPS is a well established technique worldwide to treat portal hypertension

complications. Image guided parenchymal shunt is created between systemic and

portal circulation to decrease the portal pressure.

If the shunt is created between the hepatic vein and portal vein it is called as TIPS,

most commonly right hepatic vein is used.

If the shunt is created between the IVC and portal vein it is called as DIPS.

Main complication of the procedure is shunt malfunction which can be due to shunt

occlusion or shunt stenosis (28). In the initial days with the use of bare metal stents

shunt failure rate was much higher. With the introduction of covered stents shunt

patency has significantly improved (28).Which in turn has increased the symptom free

period, has reduced the need of multiple shunt revisions and has reduced the mortality.

Various stent grafts materials are recommended, of which e-PTFE lined Gore Viatorr

stent is most commonly used stent. This e-PTFE covering helps in preventing passage

of bile in to the stent and also prevents instent parenchymal protrusion. Both these

make the stent highly non thrombogenic (28). Various studies were done to compare

patency rate of Gore Viatorr and bare metal stents. Over a time Gore Viatorr has

emerged as a stent with much better patency rate. A large multicenter study was done

in Italy for 113 patients which showed primary patency rate of Gore Viatorr to be

92% at 6 months, 80% at 1 year and 76% at 2 years (2).

85

Gore Viatorr was introduced in 1999, after European multicenter trial, available since

2001, FDA approval in December 2004 (24). In India it is available since 2005.

Gore Viatorr stent is not available in India since 2015, hence in our department Niti-S

stent is been used instead till date. English literature available about Niti-S TIPS stent

patency and clinical outcome are sparse and furthermore no Indian study is available.

Hence comparision between Gore Viatorr and Niti-S stents was done in terms of

clinical outcome, primary and secondary patency rates.

In our study total 81 patients with stent grafts were analysed. 45 patients had Gore

Viatorr and 36 patients had Niti-S stent placement. In all the patients with Gore

Viatorr stent TIPS procedure was done before 2015, hence all this data was

retrospectively analysed. Patients with Niti-S stent placement form July 2016 to

August 2017 underwent prospective analysis.

Variables studied were age, sex, pre and post TIPS pressure, clinical outcome,

Doppler findings, catheter venogram findings, number of shunt revisions needed and

death of the patients.

Post TIPS these patients had a regular follow up at 1 week, 1 month, 3 month, 6

month, 1 year and every 1 year thereafter. Regular follow up included clinical and

Doppler examination. Shunt patency was determined by combining clinical findings,

Doppler findings and catheter venogram findings.

Shunt malfunction was either due to shunt occlusion or shunt stenosis. Those patients

who had shunt stenosis were treated with balloon angioplasty.

86

Those patients with shunt occlusion were treated with thrombolysis/ thrombectomy

and balloon angioplasty.

Mean follow time for Gore Viatorr patients was 7 years +/- 1 year and for Niti-S

patients was 1.1 years +/- 2 months.

Patency rates were determined using survival analysis (Kaplan Meier curves).Primary

patency rate of Gore Viatorr stent at 3 month, 6 month, 9 month, 1 year and 2 years

were 96.4%, 92.7%, 88.9%, 88.9%, 76.7% respectively.

Primary patency rate of Niti-S stent at 3 month, 6 month, 9 month, 1 year and 2 years

were 80.8%, 70.7%, 70.7%, 50.5%, 37.9% respectively. Association between patency

rates was calculated using chi square test which showed that there is significant

difference between these two groups.

Secondary patency rates of Gore-Viatorr at 3 month, 6 month, 9 month, 1 year and 2

years were 96.9 %, 92.9%, 89%, 85%, 75.9% respectively. Secondary patency rate of

Niti-S at 1and 2 years was 75%. But statistical analysis did not show any significant

difference between the secondary patency rate of both stents.

Post TIPS survival rate in Gore Viatorr at 3month to 1 year, 2 years and at 3 to 10

years was 97.9%, 92.9%, 82% respectively. Post TIPS survival rate in Niti-S at

3month to 1 year, 2 years and at 3 to 10 years was 86%.Statistically there was no

significant difference between the two groups

87

Comparison with other studies:

Comparisons of patency rates of Gore-Viatorr was made with an Italian study

published in August 2005(28).

Time

Primary patency rate (%)

Our study

(n=45)

Primary patency rate (%)

Italian study

(n=113)

3 months

96.4%

-

6 months

92.7%

91.9%

1 year

88.9%, %

79.9%

2 years

76.7%

75.9%

Italian study had a sample size of 113 as against 45 for Gore Viatorr patients in our

study. Most common cause of portal hypertension was viral hepatitis with 58 patients

accounting for 51% of cases in Italian study whereas in our study it was Budd Chiari

syndrome with 33 patients accounting for 73% of cases. Italian study had only 2

patients with Budd Chiari syndrome. In Italian study most common indication of TIPS

was refractory ascites followed by variceal bleeding with 52 and 49 cases each

Table 12: comparing primary patency rates for Gore Viatorr stent

in our study and Italian study

88

accounting for 45% and 43%. In our study most common cause of indication was

refractory ascites accounting for 80% of cases.

In the reference study 3 month primary patency rate was not calculated, 6 month and 2

year primary patency rates were similar to our study. 1 year primary patency rate in

our study was better (88.9%) compared to the reference study (79.9%) the cause for

which is not obvious. Secondary patency rate was 98.2%, but the time interval was not

described, hence exact comparison of the secondary patency rates could not be done.

Comparison of primary patency rates for Niti-S stent were made with Korean study

published in March 2002(25) and Italian study done in June 2004 (30).

Time

Primary patency

rate (%)

Our study

Primary patency rate

(%)

Korean study

(March 2002)

Primary patency rate

(%)

Italian study

(June 2004)

3 months

80.8%

-

-

6 months

70.7%

77%

-

1 year

50.5%

72%

83.8%

Table 13: comparing primary patency rates for Niti-S stent in our study,

Korean and Italian study

89

Time

Secondary patency

rate (%)

Our study

Secondary patency

rate (%)

Korean study

(March 2002)

Secondary patency rate

(%)

Italian study

(June 2004)

1 year

-

-

98%

2 year

75%

95.4%

---

In Korean study with sample size of 22, most common cause of indication for TIPS

was variceal bleeding. In our study with sample size of 37 for Niti-S group of patients,

most common cause of indication for TIPS was refractory ascites. In Korean study

most common cause for portal hypertension was viral hepatitis accounting for 18

patients followed by alcoholic liver disease accounting for patients, this study did not

have any patient with Budd Chiari syndrome syndrome. In our study most common

cause for portal hypertension was Budd Chiari syndrome syndrome, 23 patients had

Budd Chiari syndrome syndrome, 7 patients had alcoholic liver disease and only 3 had

viral hepatitis as against 18 patients in Korean study. In Korean study primary patency

rates at 3 months was not calculated. Compared to this study, our study showed lower

primary patency rates at 6 months and 1 year and lower secondary patency rate at 2

years.

90

Italian study had sample size of 53 which was larger than our study. Most common

cause of indications for TIPS and cause of portal hypertension were variceal bleeding

and viral hepatitis respectively as against our study, but was similar to the above

Korean study. Italian study had only 2 patients of Budd Chiari syndrome accounting

for only 3.7% of patients as against our study where Budd Chiari syndrome accounted

for 63.8 of patients.

Primary patency rate and secondary patency rate at only 1 year was calculated. In

comparision our study showed lower patency rates.

Most common cause of portal hypertension in our study was Budd Chiari syndrome .

Out of total 81 patients 56 had Budd Chiari syndrome accounting for 69% of cases.

Out of total 18 patients who had shunt malfunction, 16 had Budd Chiari syndrome as

a cause of portal hypertension, 1 had alcoholic liver disease and 1 had cryptogenic

fibrosis. Out of total 18 patients, 4 were diagnosed to have hypercoagulable state. Out

of this remaining 14 patients 12 had Budd Chiari syndrome and 2 had other causes. As

Budd Chiari syndrome can result due to underlying hypercoagulable state, which can

be possibly one of the cause for higher shunt malfunction and lower patency rates in

our study.

91

LIMITATIONS:

1) Sample size as calculated could not be achieved due to the time availability.

Further recruitment of this study is ongoing.

2) Many patients were lost to follow up which is an obvious limitation of the study.

3) All the patients who had shunt block were not evaluated for hypercoagulable state

which can be possibly one of the cause of lower patency rates in Niti-S group in

our study.

4) Additional Fluency stent was placed in patients who had Gore-Viatorr in 3

patients of this 1 patient had shunt malfunction at 4 year post TIPS, this is was not

analysed separately.

92

CONCLUSIONS:

1) Primary patency rate of Gore-Viatorr at 3 months is 94.6 % and that of Niti-S is

80.8%.

2) Secondary patency rate of Gore Viatorr at 24 months is 76% and that of Niti-S is

75%.

3) Overall clinical outcome and primary patency rate of Gorre Viatorr stent is better

than Niti-S stent.

4) Secondary patency rates of Gore Viatorr and Niti-S at 24 months are similar.

93

REFERENCES:

1. Eesa M, Clark T. Transjugular intrahepatic portosystemic shunt: state of the art.

Semin Roentgenol. 2011 Apr;46(2):125–32.

2. Rösch J, Hanafee WN, Snow H. Transjugular Portal Venography and Radiologic

Portacaval Shunt: An Experimental Study. Radiology. 1969 Apr 1;92(5):1112–4.

3. Colapinto RF, Stronell RD, Birch SJ, Langer B, Blendis LM, Greig PD, et al.

Creation of an intrahepatic portosystemic shunt with a Grüntzig balloon catheter.

Can Med Assoc J. 1982 Feb 1;126(3):267–8.

4. Rössle M. TIPS: 25 years later. J Hepatol. 2013 Nov;59(5):1081–93.

5. Pomier-Layrargues G, Bouchard L, Lafortune M, Bissonnette J, Guérette D,

Perreault P. The Transjugular Intrahepatic Portosystemic Shunt in the Treatment

of Portal Hypertension: Current Status. Int J Hepatol [Internet]. 2012 [cited 2017

Jul 22];2012. Available from:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408669/

6. Fanelli F. The Evolution of Transjugular Intrahepatic Portosystemic Shunt: Tips.

ISRN Hepatol [Internet]. 2014 Mar 18 [cited 2017 Jul 22];2014. Available from:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890882/

7. Rosado B, Kamath PS. Transjugular intrahepatic portosystemic shunts: an update.

Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc.

2003 Mar;9(3):207–17.

8. Krajina A, Hulek P, Fejfar T, Valek V. Quality Improvement Guidelines for

Transjugular Intrahepatic Portosystemic Shunt (TIPS). Cardiovasc Intervent

Radiol. 2012 Dec 1;35(6):1295–300.

9. Siramolpiwat S. Transjugular intrahepatic portosystemic shunts and portal

hypertension-related complications. World J Gastroenterol WJG. 2014 Dec

7;20(45):16996–7010.

10. Rosado B, Kamath PS. Transjugular intrahepatic portosystemic shunts: an

update. Liver Transpl. 2003 Mar 1;9(3):207–17.

11. Fidelman N, Kwan SW, LaBerge JM, Gordon RL, Ring EJ, Kerlan RK. The

Transjugular Intrahepatic Portosystemic Shunt: An Update. Am J Roentgenol.

2012 Oct 1;199(4):746–55.

12. Rössle M, Olschewski M, Siegerstetter V, Berger E, Kurz K, Grandt D. The

Budd-Chiari syndrome: outcome after treatment with the transjugular intrahepatic

portosystemic shunt. Surgery. 2004 Apr;135(4):394–403.

94

13. Lv Y, He C, Guo W, Yin Z, Wang J, Zhang B, et al. Transjugular Intrahepatic

Portosystemic Shunt for Extra-Hepatic Portal Venous Obstruction in Children. J

Pediatr Gastroenterol Nutr. 2015 Sep 16;

14. Copelan A, Kapoor B, Sands M. Transjugular Intrahepatic Portosystemic

Shunt: Indications, Contraindications, and Patient Work-Up. Semin Interv Radiol.

2014 Sep;31(3):235–42.

15. Luo S-H, Chu J-G, Huang H, Yao K-C. Effect of initial stent position on

patency of transjugular intrahepatic portosystemic shunt. World J Gastroenterol.

2017 Jul 14;23(26):4779–87.

16. Suhocki PV, Lungren MP, Kapoor B, Kim CY. Transjugular Intrahepatic

Portosystemic Shunt Complications: Prevention and Management. Semin Interv

Radiol. 2015 Jun;32(2):123–32.

17. Thrombosis after transjugular intrahepatic portosystemic shunt: an ominous

sign? - Lv - AME Medical Journal [Internet]. [cited 2017 Aug 23]. Available

from: http://amj.amegroups.com/article/view/3740

18. Rössle M, Siegerstetter V, Huber M, Ochs A. The first decade of the

transjugular intrahepatic portosystemic shunt (TIPS): state of the art. Liver. 1998

Apr;18(2):73–89.

19. Ducoin H, El-Khoury J, Rousseau H, Barange K, Peron J, Pierragi M, et al.

Histopathologic analysis of transjugular intrahepatic portosystemic shunts.

Hepatology. 1997 May 1;25(5):1064–9.

20. Comprehensive Review of TIPS Technical Complications and How to Avoid

Them : American Journal of Roentgenology : Vol. 196, No. 3 (AJR) [Internet].

[cited 2017 Sep 25]. Available from:

http://www.ajronline.org/doi/full/10.2214/AJR.10.4819

21. Maleux G, Nevens F, Wilmer A, Heye S, Verslype C, Thijs M, et al. Early and

long-term clinical and radiological follow-up results of expanded-

polytetrafluoroethylene-covered stent-grafts for transjugular intrahepatic

portosystemic shunt procedures. Eur Radiol. 2004 Oct;14(10):1842–50.

22. Kim HK, Kim YJ, Chung WJ, Kim SS, Shim JJ, Choi MS, et al. Clinical

outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension:

Korean multicenter real-practice data. Clin Mol Hepatol. 2014 Mar;20(1):18–27.

23. Cejna M. Should Stent-Grafts Replace Bare Stents for Primary Transjugular

Intrahepatic Portosystemic Shunts? Semin Interv Radiol. 2005 Dec;22(4):287–99.

24. Yoon CJ, Chung JW, Kim HB, Lee JW, Park JH. A new nitinol monofilament

stent: early experience with use for transjugular intrahepatic portosystemic shunts.

Cardiovasc Intervent Radiol. 2002 Jun;25(3):200–4.

95

25. Wang C-M, Li X, Fu J, Luan J-Y, Li T-R, Zhao J, et al. Construction of

Transjugular Intrahepatic Portosystemic Shunt: Bare Metal Stent/Stent-graft

Combination versus Single Stent-graft, a Prospective Randomized Controlled

Study with Long-term Patency and Clinical Analysis. Chin Med J (Engl). 2016

Jun 5;129(11):1261–7.

26. Wang L, Xiao Z, Yue Z, Zhao H, Fan Z, Zhao M, et al. Efficacy of covered and

bare stent in TIPS for cirrhotic portal hypertension: A single-center randomized

trial. Sci Rep. 2016 Feb 15;6:srep21011.

27. McNaughton DA, Abu-Yousef MM. Doppler US of the Liver Made Simple.

RadioGraphics. 2011 Jan 1;31(1):161–88.

28. Vignali C, Bargellini I, Grosso M, Passalacqua G, Maglione F, Pedrazzini F, et

al. TIPS with Expanded Polytetrafluoroethylene–Covered Stent: Results of an

Italian Multicenter Study. Am J Roentgenol. 2005 Aug 1;185(2):472–80.

96

ANNEXURES:

Annexure 1a: Information sheet and consent form in English

Department of Radiodiagnosis, Christian Medical College, Vellore

Study Title: Comparison of efficacy of different stents used for TIPS procedure

INFORMATION SHEET PATIENT

You are being requested to participate in a study to compare the clinical outcome and

patency rates of different types of stents used in TIPS procedure. Only a particular

type of stent called Niti-S stent is used in Department of Radiology, CMC Vellore

since last year due to non availability of Viatorr Gore stent in India. At the end of

study we may be able to tell which stent has the best clinical outcome and patency

rate. Also we may be able to provide better information about clinical outcome and

patency rate of Niti-S stent as very less information is available about this stent.

What additional tests do I have to go through if I take part in this study?

If you take part in this study, you will have to come for regular follow up in OPD and

also undergo frequent Doppler scans as prescribed by your clinician. You will not

have to pay any additional amount.

Does Doppler have any side effects?

Doppler does not have any harmful radiation. We will be doing it the same way as you

would have it if you were not included in this study but more frequently

If I take part in this study, what will I have to do?

If you agree to participate in this study, there will be no change in the other

investigations and treatment that you will be receiving. You will be expected to come

to the OPD and for the Doppler scan as advised by your doctor. No additional blood

tests will be done as a part of this study.

Can I withdraw from this study after it starts?

Your participation in this study is entirely voluntary and you are also free to decide to

withdraw permission to participate in this study. If you do so, this will not affect your

usual treatment at this hospital in any way.

97

What will happen if I develop any study related injury?

This scan does not involve harmful radiation and it is non- invasive. So, we do not

expect any major procedure related injury. However you can immediately report to us.

Will I have to pay for the additional tests?

Doppler scan is usually done as a part of your routine tests. You will not have to pay

any additional amount than that is required. All other investigations, as requested by

your doctor will continue in the usual manner. How much you pay for these

investigations will not change and this has nothing to do with your participation in this

study.

What happens after the study is over?

You will benefit from this study as you will be regularly followed up, any problem

will be identified early and necessary treatment will started. Once the study is over,

we will analyze the results and come to a conclusion and we will be able to use these

results and find out which stent has the best clinical outcome and patency rate. Also

we may be able to provide better information about clinical outcome and patency rate

of Niti-S stent as very less information is available about this stent.

Will my personal details be kept confidential?

The results of this study will/may be published in a medical journal but you will not

be identified by name in any publication or presentation of results. However, your

medical record may be reviewed by doctors associated with the study, without your

additional permission.

If you have any further questions, please contact Dr. Manisha Mane (Tel: 0416

228-3012/2027/3609) between 8am & 4:30pm from Monday to Friday and from

8am to 12:30pm on Saturday or you can email your queries to

[email protected] .


98

CONSENT TO TAKE PART IN TIPS RELATED STUDY

Study Title: Study Title: Comparison of efficacy of different stents used for TIPS

procedure

Serial Number:

Patient’s name:

Hospital No:

Date of Birth / Age (in years):

(Please tick boxes)

(i) I ______________________declare that I have read / been read to the information

sheet provided to me regarding this study and have clarified any doubts that I had. [ ]

(ii) I also understand that my participation in this study is entirely voluntary and that I

am free to withdraw permission to continue to participate at any time without

affecting patient’s usual treatment or legal rights [ ]

(iii) I understand that study staff and institutional ethics committee will not need my

permission to look at patient’s health records if I withdraw from the trial. I agree to

this access [ ]

(iv) I agree not to restrict the use of any data or results that arise from this study

provided such a use is only for scientific purpose[ ]

(v) I understand that patient’s identity will not be revealed in any information released

to third parties or published [ ]

(vi) I voluntarily agree to take part in this study [ ]

Name :

Signature/ Thumb Impression

Date:

Name of witness

Signature / Thumb impression

Date

99

Annexure 2: Proforma for data collection


COMPARISION STUDY OF DIFFERENT STENTS USED FOR TIPS

1. Serial number:

2. Name of patient:

3. Age/ Sex:

4. Hospital number:

PROFORMA

5. Date of TIPS procedure:

6. Indication for TIPS:

i. Refractory ascites

ii. Refractory hydrothorax iii. Variceal bleeding

iv. Bridge to Liver transplant

7. Cause of portal hypertension:

i. Budd Chiari syndrome ii. Alcohol

iii. HBV/HCV

iv. Others (NAFLD, Cryptogenic, non cirrhotic portal hypertension)

8. Type of stent used:

i. Gore Viatorr

ii. Niti‐S:

9. Length and diameter of the stent:

100

10. Post procedure follow up to one week: I. Symptoms: a) no new symptoms b)

worsening of symptoms II. Doppler: a) patent b) block c) Velocity within shunt: at

portal end‐‐‐‐‐, mid stent‐‐‐‐, caval end‐‐‐‐ i. between 90‐190 cm/sec (normal) ii. below

90 cm/sec (abnormal) iii. above 190 cm/sec (abnormal)

I. Symptoms: a) no new symptoms b) worsening of symptoms

II. Doppler: a) patent b) Thrombosed

c) Velocity: at portal end‐‐‐‐‐, mid stent‐‐‐‐, caval end‐‐‐‐ i. between 90‐190 cm/sec

ii. below 90 cm/sec

iii. above 190 cm/sec

III. If stent thrombosis: Treatment details like thrombolysis, balloon plasty or another

stent placement

11. Follow up at 1‐2months:


II. Doppler: a) patent b) block

c) Velocity within shunt: at portal end‐‐‐‐‐, mid stent‐‐‐‐, caval end‐‐‐‐

i. between 90‐190 cm/sec (normal)

ii. below 90 cm/sec (abnormal)

iii. above 190 cm/sec (abnormal)

d) Velocity within main portal vein:

i. Above 30cm/sec (normal)

ii. below 30cm/sec (abnormal) III. Catheter venogram: a) Normal b) Stenosis c)

Occluded

IV. Balloon angioplasty: a) done b) Not required

V. New stent placed: Yes /No

12. Follow up at 3‐4 months: I. Symptoms: a) no new symptoms b) worsening of

symptoms II. Doppler: a) patent b) block c) Velocity within shunt: at portal end‐‐‐‐‐,

mid stent‐‐‐‐, caval end‐‐‐‐ i. between 90‐190 cm/sec (normal) ii. below 90 cm/sec

(abnormal) iii. above 190 cm/sec (abnormal) d) Velocity within main portal vein: i.

Above 30cm/sec (normal) ii. below 30cm/sec (abnormal) III. Catheter venogram: a)

101

Normal b) Stenosis c) Block IV. Balloon angioplasty: a) done b) Not required V. New

stent placed: Yes /No

13. Follow up at 6‐7 months:









ii. below 30cm/sec (abnormal) III. Catheter venogram: a) Normal b) Stenosis c) Block



14. Follow up at 12‐13 months: d) Velocity within main portal vein: i. Above

30cm/sec (normal) ii. below 30cm/sec (abnormal) III. Catheter venogram: a) Normal

b) Stenosis c) Block IV. Balloon angioplasty: a) done b) Not required V. New stent

placed: Yes /No

15. Follow up at One and half year :









102




16. Follow up at 2 years :












17. Balloon angioplasty done or not

I. Yes

II. No

If yes follow after balloon angioplasty:







103

d) velocity within main portal vein:


ii. below 30cm/sec (abnormal) III. Catheter venogram: a) Normal b) Stenosis c)

Occluded


18. Lost to follow up

19. Death of patient: Yes/NO If yes: cause of death

104

Annexure 3: IRB protocol

Title of Research Project:

Institutional Review Board application form, Version 2.6, Sep 2015 Page 1

APPLICATION FOR IRB APPROVAL OF OBSERVATIONAL

(CASE-CONTROL / COHORT/ CROSS-SECTIONAL) STUDIES

CHRISTIANMEDICALCOLLEGE, VELLORE

(Please complete Sections I to III and submit with all supporting documents)

SECTION I

Fluid Research Funding/External Funding (delete as appropriate)

If for external funding, please provide name of funding agency and the

application

for submission in the funding agency’s format, in addition to this application.

1. Title of Research: Comparison of clinical outcome and patency of Gore-Viatorr

and Niti-S stents

used in Transjugular intrahepatic portosystemic shunt (TIPS)

2. Title of Study(for lay public): A study to evaluate which is the best stent for

Transjugular

intrahepatic portosystemic shunt procedure

3. Acronym if any: Nil

4. Unique Protocol ID, if any: Nil

5. Name of the Principal Investigator: Dr. Manisha Sheshrao Mane

Designation / Department / Unit / of Principal Investigator: 1st year PG,

Radiology

Department

Employment Number: 33298

Address for communication (including telephone and fax numbers and email id):

105

2D4-House no 60, CMC Nursing college campus, Kagithepetterai, Vellore 632004

Mobile number: 9655992163

If Post Graduate Registrar: Yes

Enrollment date of PG Course: 01/04/2015

Completion date of PG Course: 30/03/2018

6. Name of Guide (for Post-Graduate Registrar / Fellowship):

Dr. Munawwar Ahmed



Associate Proffesor,

Christian medical college, Vellore,

Employment Number: 32015

Address for communication (including telephone and fax numbers and email id):

Telephone: 0416307 3012/ 3609

Email id: [email protected]

7. Name and Designation of Co-Investigator(s), Employment Number and

Address :

Dr. Shyamkumar N. Keshava

Professor and Head,

Department of Radiology,

Christian Medical College Hospital,

Ida Scudder road,

Vellore

India. 632004

[email protected]

[email protected]

106

Dr. Vinu Moses

Professor,


Christian Medical College,

Vellore, Tamil Nadu.

Employment number: 28371


Dr. George Koshy Chiramel

Associate professor,


Christian Medical College Hospital,

Ida Scudder road

Vellore

India. 632004

Dr. C.E.Eapen

Professor and Head of Clinical Gastroenterology and Hepatology,




Contact number: 2496 / 2148

Dr. Uday George Zachariah,



Professor and Acting Head of Hepatology,



107



Dr. Ashish Goel

Professor of Hepatology,



EMP no. 31642



8. Department of Institution where the research will be carried out: Department

of Radiodiagnosis,

CMC Vellore, 632004

9. Names and addresses of other institutions where research will be carried out:

Nil

10. Duration of the Scheme: 13-14 months

11.Source/s of Monetary or Material Support

Internal - Fluid /Major Research Grant: Yes

External : Nil

Departmental fund : Nil

12.Permission letter from the HOU & HOD of each unit/department involved in

the study. If Medical students, Nursing students & Allied Health students,

nurses, are involved in the study a permission letter from the appointing

authority has to be enclosed: Not applicable

13. If this is a laboratory study if you have out sourced genetic test to be an

external laboratory. Please provide evidence of the laboratory credentials.

Not applicable

108



14. Is this an invention or idea that you plan to register as a

patient: No

15. Objectives and aims of study (including any hypotheses).

® To compare primary patency at 3 months and secondary patency rates at 24 months

of Viator

Gorre and Niti-S stents

® Which stent has the best primary patency rate?

® To compare clinical outcome of Gore-Viatorr and Niti-S stents

16. Summary of the proposed research scheme (250 words).

In the Department of Radiology, CMC Vellore various stents such as Uncovered,

Gore Viatorr, Uncovered-Covered and Niti-S TIPS stents have been used. In the year

of

2015 only Niti-S TIPS stent was used due to non-availability of Gore Viatorr stent in

India.

® In this study comparison of clinical outcome and primary and secondary

patency of Gore-Viatorr and Niti-S stents will be conducted. All the patients who

have undergone TIPS procedure in Department of Radiology and patients

undergoing TIPS for next 1 and half years will be included in this study.

Data from the year of 1999 will be collected and retrospectively analyzed, whereas

Data collected from patients undergoing TIPS for next 1 and half years will be

prospectively analyzed.

17. Present Knowledge and relevant bibliography (Is there a justification for this

study based

on a detailed literature review or other sources of evidence? Please provide details)


109


Transjugular intrahepatic portosystemic shunt (TIPS) has played an important role in

managing and treating complications of portal hypertension like variceal bleeding and

refractory ascites/hydrothorax. In the early years, mortality and shunt patency due to

shunt dysfunction was high due to use of bare metal stents. Long term shunt patency

was significantly improved following introduction of covered stent (1). Amongst the

various covered stents used, Gore Viatorr stent is most commonly used stent.

Various stents used in Department of Radiology, CMC Vellore are

-Gore Viatorr stent

-Uncovered

-Covered-Uncovered

- Niti-S TIPS stent

Gore Viatorr stent:

-Introduced in 1999, after European multicenter trial, available since 2001, FDA

approval in

December 2004 (2)

-In India available since 2005

-Structural support is provided by an external self-expanding nitinol stent (4)

-Intrahepatic portion of the stent is covered with PTFE whereas the bare part lies in

the portal

vein (3)

-Covered and uncovered portion, interface is demarcated by radio-opaque gold ring(4)

-Additional radiopaque gold marker is at the proximal end which helps fluoroscopic

visualisation

during deployment (3)

Angermayr et alhave retrospectively demonstrated an improved survival rate of 88%

at 1 year for

110

patients treated with theVIATORR1 endoprosthesis for TIPS, compared with 73% for

a matched

group receiving bare stents. Survival rate after TIPS creation with the VIATORR

device is higher

than that after TIPS creation with an uncovered stent (3)

Niti-S TIPS stent:

-This stent has been used exclusively in our departmentsince 2015 onwards as Gore

Viatorr is

not available in India



-Niti-S TIPS stent is being used since 2015 onwards as Gore Viatorr is not available in

India

English literature available about Niti-S TIPS stent patency and clinical outcome are

sparse and

furthermore no Indian study is available.

-It is a mesh-type stent interlaced with a nitinol monofilament. (4)

-Nitinol monofilament wire is wound on a mandrel to create a spiral mesh at

deployment, the

stent self-expands to a predetermined diameter of 8–10 mm with a length of 6–10

cm.(4)

-It has constant 20mm uncovered portion and variable covered portion [varying from

40mm to

100mm (4)

Following are few overseas studies conducted for Niti-S TIPS stent which suggests

that primary

patency of this stent is lesser than that of Gore Viatorr stent:

A New Nitinol Monofilament Stent (Niti-S stent): Early Experience with Use for

Transjugular

111

Intrahepatic Portosystemic Shunts, Cardiovascular and Interventional Radiology, 27

March 2002

(5)

Sample size 22

Primary patency rate 77% at 6 months

72 % at 1 year

Secondary patency rate 95 % up to 26 months

Rossi P, Bezzi M, Salvatori FM, et al. (1996) Self-expanding (uncovered)stents in

Transjugular

intrahepatic portosystemic shunt: Experience with nitinol Strecker stents(Niti-S

stents),

Rome,EUR radiology 6:741–747 (6)

Sample size 48

Primary patency rate 25 to 66% at 6 months

Secondary patency rate 80-89 % at 6-24 months

Doppler evaluation: (7)

Normal Values:



Shunt velocity: >90 cm/sec or <190 cm/sec

MPV velocity: should be more than 30 cm/sec

Shunt malfunction-Doppler evaluation: (7)

® Due to narrowing or occlusion - intimal hyperplasia or insitu thrombosis

® Most common site for occlusion or stenosis is cephalic portion/portal end

® Occlusion - absent flow at colour Doppler

® Stenosis - abnormally high (>190 cm/sec) / abnormally low (<90 cm/sec) velocity

within

112

the shunt or increase or decrease >50 cm/sec compared with the prior examination

® Portal venous flow changes from hepatofugal to hepatopetal flow

® MPV-Low velocity (<30 cm/sec)

® Development or recurrence of collateral vessels such as a recanalized umbilical

vein

® New, recurrent, or worsening ascites

References:

1.Clinical outcomes of Transjugular intrahepatic portosystemic shunt for portal

hypertension:

Korean multicentrereal-practice data,

Hyung Ki Kim1,Dae Won Jun8, Moon Young Kim13, Soo Young Park14, Jae

Myeong Lee15,

and Young Seok Kim1, Yoon Jun Kim2, Soon Ho Um9, Woo Jin Chung3, Sung Jae

Park10,

Young Woo11, Young Kul Jung12, Soon Koo Baik13, Soon Sun Kim4, Jae Jun

Shim5

Department of Internal Medicine, Soonchunhyang University College of Medicine,

Bucheon; 2

Research Institute, Article in clinical and molecular hepatology, 2014

2. Should Stent-Grafts Replace Bare Stents for Primary TransjugularIntrahepatic

Portosystemic Shunts?

Manfred CM.D.,1Section of Interventional Radiology, Vienna Medical School,

Austria; and

Department of Radiology, LKH Feldkirch, Feldkirch, Austria

Seminar Intervention Radiology, 2005 Dec; 22(4): 287–299.

3. Transjugular Intrahepatic Portosystemic Shunts: An Update;



113

Editors in Chief, Brian Funaki, M.D., Peter R. Mueller, M.D.; Guest Editor, Hector

Ferral, M.D.

Seminars in Interventional Radiology, volume 22, number 4, 2005.

4. A New Nitinol Monofilament Stent: Early Experience with Use for Transjugular

Intrahepatic Portosystemic Shunts,

Chang Ji ,Radiologyn Yoon, Jin oo ChuHyun, KiJoWoo Lee, Jae Hyung Park,

CardioVascular and Interventional Radiology, 27th march 2002

5. A new Nitinol Monofilament Stent (Niti-S stent): Early Experience with Use for

Transjugular

Intrahepatic Portosystemic Shunts,

Chang Jin Yoon, Jin Wook Chung, Hyun Beom Kim, Joon Woo Lee, Jae Hyung Park

Department of Radiology and the Institute of Radiation Medicine, Seoul National

University

College of Medicine, 28 Yongon-Dong,

Cardiovasc Intervent Radiol (2002) 25:200–204

Published on 27 March 2002

6. Self-expanding stents in transjugular intrahepatic portosystemic shunt: Experience

with

nitinol Strecker stents

Rossi P1, Bezzi M, Salvatori FM, Broglia L, Maccioni F, Pizzi G, Abbondanza S,

Bonomo

G.

Department of Radiology, University of Rome La Sapienza, Policlinico Umberto I,

Italy.

EUR radiol 1996;6(5):741–7

7. Doppler US of the Liver Made Simple, Gastrointestinal imaging,

Dean Alexander McNaughton, MD, and Monzer M. Abu-Yousef, MD,

RSNA, Radiographics, January-February 2011, Volume 31, Issue 1

114

18. Preliminary work already done by the investigator in this problem :

- Retrospective pilot study was done for a period of 3 years from 2013 to 2015 for 45

patients.

- Gore Viatorr, Uncovered, Covered-uncovered, Niti-S TIPS stents were used in these

patients for TIPS procedure.



This retrospective pilot study showed that Primary patency rate of Niti-S TIPS stent at

the end of one month is less compared to other stents.

However the secondary patency rate appeared similar to Gore Viatorr Stent

19. List of publications of the investigator in the field: Nil

Retrospective pilot study, 3 years

(2013-2015)-45 patients

Gore Viatorr-14

Covered--uncovered-12

Uncovered-3

Niti-S-14



20. Structured abstract (Structured abstract should be in future tense)

® Aim: To compare the clinical outcome and patency rates of Gore-Viatorr and Niti-S

stents

used in Transjugular intrahepatic portosystemic shunt (TIPS)

® Methods: All the patients who have undergone TIPS procedure in the Department

of

Radiology, CMC Vellore from 1999 onwards will be included in the study

-All patients coming to CMC who have already undergone TIPS procedure will be

115

retrospectively analyzed

- Patients who will need TIPS will undergo prospective analysis. In these patients

NITI S

stents will be used unless Gore Viator stent becomes available

® Results:

Clinical outcome and patency rates of two different stents used for TIPS procedure

will be

compared, Primary patency rate will be calculated at the end of 1 year

We aim to determine the patency rate of the Niti-S TIPS stent, and whether it has a

better or equivalent patency rate compared to Gore-Viatorr stent

21. Detailed diagrammatic Algorithm of the study:

Patient

Clinical assessment in OPD

Doppler / CT (Radiology)

Procedure (TIPS/DIPS)

Follow up

Post procedure follow up to 1 week; 1, 3, 6 months 1st year,

every 6 monthly after 1 year

Asymptomatic &normal Doppler Symptomatic & normal Doppler Asymptomatic

&abnormal Doppler Symptomatic &abnormal Doppler

Follow up Follow up

Catheter venogram

Normal Abnormal



22. Detailed research plan:

a. Setting: Describe the setting, locations, and relevant dates, including periods of

116

recruitment, exposure, follow-up, and data collection

Patients who have already undergone TIPS procedure from 1999 onwards in the

Department of Radiology, CMC Vellore will be included in the study.

Patients who will undergo TIPS procedure for next 13-14 months will also be

included in the study.

Data collected from 1999 onwards will be retrospectively analysed

Data collected from patients undergoing TIPS procedure with Niti-S stent for next

13-14 months will be prospectively analysed

Participants: Give the eligibility criteria, and the sources and methods of case

ascertainment and control selection. Give the rationale for the choice of cases (and

controls, if applicable). For matched studies, give matching criteria and the number

of controls per case

Patients who have already undergone TIPS procedure from 1999 onwards will be

included in the study and retrospectively analysed.

Patients who will undergo TIPS procedure for next 13-14 months will also be

included in the study and will undergo prospective analysis.

b. Variables: Clearly define all outcomes, exposures, predictors, potential

confounders, and effect modifiers. Give diagnostic criteria, if applicable

Efficacy of various stents will be analysed based on following parameters:

Outcome will be measured in the form of Clinical outcome, Doppler and Catheter

venogram

findings, Shunt blockage, number of shunt revisions required and death of the

patient

Potential confounders are age, severity of cirrhosis of liver and cause of cirrhosis

of liver as patients with Budd Chiari tend to be younger and patients with alcoholic

liver disease and cirrhosis secondary to HBV/HCV infection tend to be older and

117

have more severe cirrhosis of liver

There are no effect modifiers in this study

Follow up Balloon angioplasty

Follow up



c. Data Sources/measurement: For each variable of interest, give sources of data

and details of methods of assessment (measurement). Describe comparability of

assessment methods if there is more than one group

1. Clinical outcome will be analysed in terms of whether there is decrease in

symptoms, onset of new symptoms or worsening of symptoms.

2. Doppler evaluation of the shunt, whether it is patent or blocked, velocities within

the shunt and main portal vein.

Shunt velocities will be taken at portal end, mid shunt and caval end. Velocities

should be within 90-190 cm/sec range. Velocity above below 90 and above 190

will be considered abnormal.

Main portal vein velocity should be above 30 cm/sec, velocities below

30cm/sec will be considered abnormal.

Doppler evaluation will be part of a routine procedure

3. Catheter venogram: If the patient is symptomatic and Doppler is abnormal patient

will be

called for follow up

If patient is symptomatic and Doppler is abnormal or if patient is asymptomatic

and Doppler is abnormal patient will undergo Catheter venogram

4. Balloon angioplasty: If Catheter venogram findings are abnormal patient will

undergo

118

balloon angioplasty and then will be followed up

d. Bias: Bias may arise due to loss of follow up of patients and may affect analysis.

Many of the patients who will undergo retrospective analysis have not followed up

in CMC, we will maximize the input by calling them and reviewing their outside

reports and scans

e. Sample size:(It may be suitable to have a statistician as a co-investigator)

The required sample size to compare the primary patency rates across Viator

Gorre and Niti-S stents used in Transjugular intrahepatic portosystemic shunt

(TIPS) was found to be 49 in each of the groups with 80% power and 5% level of

significance when the expected difference in the patency rates was considered as

30%. However, the number of available Niti-stents are only 45 so far from the year

2000.

Also, we expect only about 25 – 30 cases more of Gore-Viatorr in the next 3 – 4

months. Hence this study will include all the available cases of Niti and Viator

Gorre stents.

The above patency rates were obtained using the following references:



A New Nitinol Monofilament Stent (Niti-S stent): Early Experience with Use for

Transjugular Intrahepatic Portosystemic Shunts, Cardiovascular and Interventional

Radiology, 27 March 2002

Rossi P, Bezzi M, Salvatori FM, et al. (1996) Self-expanding (uncovered)stents in

Transjugular intrahepatic portosystemic shunt: Experience with nitinol Strecker

stents(Niti-S stents), Rome,EUR radiology 6:741–747 (6)

Formula:

Where, P1 = 77%

119

P2 = 50%;

Power = 80%; , Level of significance = 5%

Reference for the above formula: Sahai H, Kurshid A.

Formulae and tables for the determination of sample size and power in clinical

trials for testing differences in proportions for the two sample design: a review.

Statistics in Medicine, 1996; 15: 1-21.

Two Proportion - Hypothesis Testing - Large Proportion - Equal Allocation

Proportion in group (primary patency rate in

Gore-Viatorr) 0.77 0.77 0.7 0.7 0.7 0.7

Proportion in group (primary patency rate

in Niti S stents) 0.66 0.5 0.6 0.55 0.5 0.45

Estimated risk difference 0.11 0.27 0.1 0.15 0.2 0.25

Power (1- beta) % 80 80 80 80 80 80

Alpha error (%) 5 5 5 5 5 5

1 or 2 sided 2 2 2 2 2 2

Required sample size for each arm 263 49 35 6 93 60

Allocation

f. Quantitative variables: Explain how quantitative variables will be handled in the



analyses. If applicable, describe which groupings were chosen and why

Age is the only continuous variable and it will be presented using mean with SD in

both typed of stents. The age of the patients across the two stents will be

compared using Independent t-test or Rank sum test whose choice will be based

on the QQ plot.

g. Statistical methods: Describe all statistical methods, including those used to

120

control for confounding and examine subgroups and interactions. How will missing

data be handled? If applicable, how will matching of cases and controls be

handled? Describe any proposed sensitivity analyses.

-Primary patency rate and secondary patency rate will be presented as percentage (%)

for

two groups.

-All Binary outcomes such as primary and secondary patency rates (symptoms,

Doppler

findings, Catheter venogram findings) will be presented in both the stents as a

frequency table and

percentages with 95% CI. They will also be shown and also by using bar plot.

-Comparison between the groups will be performed using Z test for 2 sample

proportion

test.

-Association between patency rate and clinical outcome will be performed by using

chi

square test. Logistic regression will also be used to find the association of patency rate

with clinical outcomes adjusting for confounders if any.



i. Name & designation of the statistician involved in your project for Statistical

Analyses:

Dr. Visalakshi Jeyaseelan

Emp. Number 31093

Dept. of Biostatistics, CMC, Vellore.

23.Complete budget plan

For FLUID research grant money cannot be allocated for travel of the investigators

121

nor can job outsourcing be covered with FLUID grants. Funding out of the

institution

can be given only for the special mission hospital grant

(From Fluid Research Fund, there are no grants for personnel except in a major

grant

application, funding is limited Rs. 50,000/- per year for two years for standard

applications,

Rs. 2,00,000/- per year for two years for major applications). Website link:

http://172.16.11.136/Research/#. >Rules for Major Fluid Research Grants. Do not

exceed

the budget allocated to you. In case the budget is exceeded, the amount will have to be

deducted from one of your departmental special funds. Stationary, printing material

and

paper should not exceed more than 20% of the allocated fluid grant.

Please mention below the breakdown of budget requested: (The budgets that are

drawn up should becomprehensive and should mention all subject in detail (For

example

– laboratory investigation should mention the specific category without

generalization.)

Serial No ITEM Cost Number of

patients

Total

1. Doppler 2 x 2900 16 92,800

2. Stationary/ Printing/

Binding

6000 - 6000

Total Total = Rs.98,800/-

24. Enclose proforma for Data collection:

122



Enclosed

25. If this is an application for Fluid Research Funding, please provide name and

account number of any other Fluid Research grant held by the PI.

Fluid research grant applied

S. No Study Title IRB Min. No.

and date

Grant Sanctioned

amount/ Account Head

Duration /

Year

Study ongoing/

completed

26. Informed Consent Documents (patient information sheet, investigator’s

brochure,

drug information etc and informed consent document) please submit all

translations with the

proposal.

Enclosed

We request waiver of consent for the retrospective group

Consent for the prospective group will be taken before the procedure

27. Publication Plans: (List all potential authors and their likely contributions)

(Please tick √ appropriate box)

Responsibilities

Author(s)

123

Name

Research

and

Study

design

Data

collection

& analysis

Lab

analysis

Interpretation

and

conclusion

Preparation

of

Manuscript

Review

of

Manuscript

Guide

And

critical

revision

Administration Technical

Support

Dr. Manisha Mane √ √ - √ √ √ √ - -

124

Dr.Munawwar Ahmed √ √ - √ √ √ √ - -

Dr.Shyamkumar N.

Keshava

√ √ - √ - √ √ - -

Dr. Vinu Moses √ √ - √ - √ √ - -

Dr. George Koshy

Chiramel

√ √ - √ - √ √ - -

Dr.C.E.Eapen √ √ - √ - √ √ - -



Dr.Uday George

Zachariah

√ - - √ - √ √ - -

Dr. Ashish Goel √ - - √ - √ √ - -

28. Inter-departmental cooperation: (Please describe the arrangements with

institutional

diagnostic service units/departments that are being used for this research project, if

applicable).

Patient will be clinically assessed in Hepatology OPD and DSA suite and will be sent

to

Radiology Department for Doppler evaluation

29. Signature of Principal Investigator

30. Signature of Guide/Head of the Department/ Unit

31. Co-Investigators’ Consent (all co-investigators have to sign this form or

supply

separate letters of consent)

125

I/We give my/our consent to be a Co-Investigator and provide my/our expertise to the

project.

I/We have approved this version of the protocol and have contributed substantially to

its

development.

Name Department Signature Date

Dr. Munawwar Ahmed Radiology

Dr. Shyamkumar N. Keshava Radiology

Dr. Vinu Moses Radiology

Dr. George Koshy Chiramel Radiology

Dr. C.E.Eapen Clinical Gastroenterology

and Hepatology



Dr. Uday George Zachariah Hepatology

Dr. Ashish Goel Hepatology

Note: If the project is a resubmission a fresh copy of signatures needs to be

obtained for

IRB

submission.

Section II

APPLICATION FOR APPROVAL FROM ETHICS COMMITTEE OF THE

INSTITUTIONAL

REVIEW BOARD OF CMC VELLORE FOR ALL OBSERVATIONAL (CASE

CONTROL,

COHORT & OBSERVATIONAL) STUDIES IN HUMAN SUBJECTS

1. Please provide a brief summary of the justification, objectives and methods in

lay

126

language, avoiding technical terms:

Shunt is a track created between two vessels and stent is a mesh like metal pipe which

is

placed within this track.

TIPS (Transjugular portosystemic shunt) is a procedure where a track is created

between the

IVC/hepatic vein and portal vein which helps to reduce the portal pressure and tubular

mesh

like metallic device is placed in this track which is called stent .

It is a useful treatment for patients suffering from symptoms of portal hypertension

like fluid

accumulation in various parts of the body ie abdomen and chest, bleeding from mouth

which

is not responding to the regularly used treatment

Different types of Stents are used for this procedure, In our study we want to find out

whether

Gore Viatorr or Niti-S stent is better

Very less information is available about Niti-S stent, at the end of the study we will be

able to

provide more information about Niti-S stent

2. Please describe if the study uses procedures already being performed on

patients for

diagnosis or treatment or if modified or novel procedures are to be used?

Study uses procedures all being performed on patients



3. Please describe what benefits might be reasonably be expected by the

participant as

an outcome of participation

127

-Only a particular type of stent called Niti-S TIPS stent is used in Department of

Radiology,

CMC Vellore since last year due to non-availability of Gore Viatorr stent

-Very few overseas studies and no Indian study is available for Niti-S TIPS stent

-We aim to find out which type of stent doesn’t get block early and hence reduces

further

treatment required for this block and death rate

-We also want to find out whether Niti-S TIPS stent is better or same as commonly

used

stents

-The participant may not get benefited directly from the study but results of study will

be

helpful for providing exact information about the Niti-S TIPS stent

4. Please describe what benefits to others or new knowledge might be expected as

a

result of this study

Results of study will be helpful for providing exact information about the Niti-S TIPS

stent

5. Who are to be enrolled?

All patients who have undergone this procedure from 1999 onwards in department of

Radiology, CMC Vellore and also who will undergo the same procedure for 13-14

months from February 2016 to April 2017 will be included in the study

6. If any vulnerable groups (e.g., pregnant women, children) are to be enrolled,

please

provide a justification for their inclusion.

Not involved

7. Mention how you will ensure that there is no undue inducement for

participation of

economically disadvantaged persons among the likely participants in this study.

128

Participants of this study will not have to pay for the study. However the rest of the

Investigations and treatment will be as decided by the treating clinician.

8. What are the potential risks to participants in this study?

There are no risks associated with this study.

9. Are the risks to participants reasonable in relation to the benefits that might

reasonably be expected as an outcome to the participant or to others, or the

importance of the knowledge that may reasonably be expected to result? Please

provide a detailed description of the above.

Not applicable



10.Regarding informed consent to obtained from research participants or their

legally

authorized representative(s):

a. Does the informed consent document include all the required elements?

Yes

b. Are the participant information sheet and the consent document in language

understandable to participants? (PLEASE PROVIDE WITH THIS

SUBMISSION

TRANSLATIONS IN ALL LOCAL LANGUAGES ANTICIPATED TO BE

USED).

Yes

c. Who will obtain informed consent (PI, nurse, other?) and in what setting?

Primary investigator will obtain informed consent before performing the ARFI study.

d. If appropriate, is there a children’s assent? If yes, please submit a copy of this

form.

Not applicable

129

e. Is the EC requested to waive or alter any informed consent requirement?

No

11. Is there provision of free treatment for research related injury? If yes, who

will

provide it?

There are no injuries related to the study

12. Is there provision for compensation of participants for disability or death

resulting

from research related injury. If yes, who will provide it?

Not applicable

13. Is the study covered by insurance? If yes, please provide insurance

documents from

an Indian insurance company.

No

14. In addition to the overall budget in Section I, please provide details of the

following

i) Justification, timing and amount of payments to study participants

Not applicable

ii) Justification, timing and amount of payments to investigators/departments

Not applicable

iii) Any other study related financial or in kind incentives to participants or

study staff

Not applicable

15. Please describe the plan for maintaining confidentiality of study participant

information.

130



All data obtained from a particular patient will have a unique identification code and

the identity of the patient will not be revealed in any manner.

Patient’s information and results of the study will not be accessible to anyone other

than those involved in the study (staff)

16. Please describe the plans for monitoring the safety of participants, reporting

and

managing adverse events. If this is an externally funded study with a Data Safety

Monitoring Board, please provide the name and contact information of the

DSMB

chairperson.

Data will be stored in a password protected computer

Only the principal investigator/co investigators will have access to the

patient data.

Patient data will be stored in a password protected computer and data will be

deleted when no longer required.

17. If applicable; please provide all significant previous decisions (e.g., those

leading to a

negative decision or modified protocol) by other ECs or regulatory authorities

for the

proposed study (whether in the same location or elsewhere) and an indication of

the

modification(s) to the protocol.

Not applicable

18.If appropriate, has permission from the Drug Controller General of India

been

obtained?

131

Not applicable

19.If this is international collaborative research, has permission from the Health

Ministry’s Screening Committee been obtained?

Not applicable

20.For exchange of biological material in international collaborative studies,

provide a Memorandum of Understanding (MOU)/ Material Transfer

Agreement

(MTA) between the collaborating partners.

Not applicable

21.Declaration (to be signed by all investigators)

By signing this form we give our consent to provide our expertise to the project. In

addition:

a. We confirm that all investigators have approved this version of the protocol and

have

contributed substantially to its development.

b. We confirm that all potential authors are included in this protocol.

c. We confirm that we shall submit any protocol amendments, significant deviations

from

protocols, progress reports (if required) and a final report and also participate in any

audit

of this study, if required.



d. We confirm that we shall conduct this study in accordance with the Declaration of

Helsinki; the ICMR Guidelines for Biomedical Research in Human Subjects 2006,

with

any subsequent amendments; and all applicable laws of the land.

132

e. We also agree to submit for publication to a peer reviewed journal the complete

results of

this study within two years of completion of this study.

f. We declare that we have no conflicts of interest that may affect the conduct or

reporting

of this study (OR) we declare the following conflicts of interest below.

g. We are aware of the institution’s policies regarding scientific misconduct

(Falsification/fabrication/plagiarism) and agree to abide by them.

22.Signature of Principal Investigator:

23.Signature of Guide/Head of the Department/ Unit:

24.Co-Investigator’s Consent (all co-investigators have to sign this form or

supply

separate letters of consent)

Name Department Signature Date

Dr. Munawwar Ahmed Radiology

Dr. Shyamkumar N Keshava Radiology

Dr. Vinu Moses Radiology

Dr. George Koshy Chiramel Radiology

Dr. C.E.Eapen Clinical Gastroenterology

and Hepatology

Dr. Uday George Zachariah Hepatology



Dr. Ashish Goel Hepatology

Note: If the project is a resubmission a fresh copy of signatures needs to be

obtained for

IRB submission.

133

Conflicts of interest if any:

SAMPLE INFORMATION SHEET & CONSENT FORM

Section III

CHECKLIST FOR PROTOCOLS SUBMITTED TO IRB OF CMC VELLORE

FOR

OBSERVATIONAL

(CASE CONTROL, COHORT & CROSS SECTIONAL) STUDIES

Please tick the appropriate boxes below to indicate that the following have been

submitted

and if not, please explain why:

1. Form for protocols of Observational Studies with all sections (I, and II) completed

[√]

2. Informed consent sheet and participant information sheetin all relevant local

languages

(PDF Format) [√ ]

3. Names, affiliations and signatures of all investigators/co-investigators for the

declaration [√]

4. Signature of the Head of the department or unit as applicable (for interdepartmental

studies, an agreement letter from concerned departmental heads is desirable,

especially if

they are not co-investigators). [√ ]

5. Recent curriculum vitae of all the investigators indicating qualification and

experience and

relevant publications in the past five years. [√ ]

6. If applicable, proposed compensation and reimbursement of incidental expenses

and

management of research related and unrelated injury/ illness during and after research

period. [Not applicable]


134


7. If applicable (in study-related injuries), a description of the arrangements for

insurance

coverage for research participants and copy of insurance documents from an India

insurance agency. [Not applicable]

8. If applicable; all significant previous decisions (e.g., those leading to a negative

decision or

modified [Not applicable]

protocol) by other ECs or regulatory authorities for the proposed study and an

indication of

the modification(s) to the protocol made on that account. The reasons for negative

decisions should be provided. [Not applicable]

9. Plans for publication of results - positive or negative - while maintaining the

privacy and

confidentiality of the study participants, with names of proposed authors and their

expected

contributions. [√]

10.All other relevant documents related to the study protocol like product information

and

statement of relevant regulatory clearances. [√]

11.If applicable, any material used for advertisement to recruit participants to the

study - this

may include flyers, brochures, posters, radio and TV advertisements. [Not applicable]

12.For externally funded studies, details of Funding agency/ Sponsors and breakdown

of fund

allocation. [Not applicable]

13.One hard copy and a soft copy on CD to [email protected] of all the

above.

[√]

135

Please list below all additional documents that are being submitted along with

this

application including all appendices.

1. CV of guide and coinvestigator: Dr. Munawwar Ahmed

2. CV of coinvestigator: Dr. Shyamkumar N. Keshava

3. CV of coinvestigator: Dr. Vinu Moses

4. CV of coinvestigator: Dr. George Koshy Chiramel

5. CV of coinvestigator: Dr. C.E.Eapen

6. CV of coinvestigator: Dr. Uday George Zachariah

7. CV of coinvestigator: Dr. Asish Goel

8. CV of principal investigator: Dr. Manisha Mane

9. Information sheet and consent form in English

10.Information sheet and consent form in Hindi

11.Information sheet and consent form in Tamil

12.Information sheet and consent form in Bengali

13.Data collection sheet (Proforma)

14.Colour Doppler : TIPS stent format



Format for Informed Consent Form for Subjects

Informed Consent form to participate in a research study

Study Title:

Study Number: ____________

Subject’s Initials: __________________ Subject’s Name:

_________________________________________


136


Date of Birth / Age: ___________________________

(Subject)

(i) I confirm that I have read and understood the information sheet dated

____________ for the above study and have had the opportunity to ask questions.

[ ]

(ii) I understand that my participation in the study is voluntary and that I amfree to

withdraw at any time, without giving any reason, without my medical care or legal

rights being affected. [ ]

(iii) I understand that the Sponsor of the clinical trial, others working on the

Sponsor’s behalf (delete as appropriate), the Ethics Committee and the

regulatory authorities will not need my permission to look at my health records both

in respect of the current study and any further research that may be conducted in

relation to it, even if I withdraw from the trial. I agree to this access. However, I

understand that my identity will not be revealed in any information released to third

parties or published. [ ]

(iv) I agree not to restrict the use of any data or results that arise from this study

provided such a use is only for scientific purpose(s).[ ]

(v) I agree to take part in the above study.[ ]

Signature (or Thumb impression) of the Subject/Legally Acceptable

Date: _____/_____/______

Signatory’s Name: _________________________________Signature:

Or

Representative: _________________



137

Date: _____/_____/______

Signatory’s Name: _________________________________

Signature of the Investigator: ________________________

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slno age sex tipsdate tipsindi porthyperhypercaogstenttypenumofstentlength1 diameter1stent2 length2 diamter2folluptil batime sympt doppler portal midstentcavalendmainportvenogramballoon newstentstenttype1

1 59 2 19/07/2005 3 3 1 1 6 10 0 1 1

2 45 1 27/02/2006 1 1 1 2 10 10 8 10 8 3 years 1 1 2 2

3 28 2 19/08/2006 1 1 1 1 10 10 8 10 3 3-4 months 1 1

4 25 2 26/02/2007 1 1 1 1 0 1 1

5 35 2 18/04/2008 1 1 1 1 10 10 6 1 year 1 1

6 18 1 20/04/2009 1 7 1 1 9 10 4 1 1 230 150

7 42 2 27/09/2009 1 1 1 1 10 10 15 1 1 2 2

8 45 1 26/08/2009 1 5 1 1 6 10 3 3-4 months 1 1

9 22 1 26/08/2009 1 1 1 2 8 10 Fluency 4 10 8 1 1

10 50 1 16/12/2009 1 2 1 1 10 10 1 1 1

11 35 2 03/02/2010 1 1 1 2 10 10 Niti-S 9 10 12 1 1

12 52 2 25/08/2011 1 1 1 1 8 10 1 1 1 207 163 203 2 2

13 76 1 16/08/2012 1 5 1 1 4 10 0 1 1 198 202 180 10 2 2

14 53 2 28/07/2010 1 1 2 1 1 8 10 7 1 1 80 30 2 2

15 62 1 05/07/2010 1 4 1 1 8 10 0 1 1 100 70

16 48 2 18/10/2010 1 1 1 1 2 10 10 fluency 4 10 9 1 1 120 130 100 30 2 1

17 35 1 17/12/2010 1 1 2 1 2 10 10 fluency 4 12 7 1 1

18 64 1 01/08/2011 1 1 2 1 1 8 10 0 1 1

19 48 1 13/12/2011 3 2 2 1 1 8 10 11 1 1 108 149 152 84 2 2

20 41 1 26/12/2011 1 1 2 1 1 10 10 11 1 1 2 2

21 24 2 21/12/2011 1 1 1 1 1 10 10 6 1 year 1 1 110 120 200 70 2 1

22 32 2 07/12/2011 1 1 2 1 1 10 10 0 1 1

23 0 1 1

24 32 2 31/08/2011 1 1 2 1 1 0

25 51 2 05/09/2011 3 5 2 1 1 8 10 6 1 1

26 35 2 21/10/2011 1 1 2 1 1 10 10 8 1 1

27 20 1 07/03/2012 1 1 2 1 1 9 10 7 2 years 1 1

28 52 2 14/03/2012 3 4 2 1 1 4 10 7 1 1 2 2

29 15 1 30/04/2012 1 1 1 1 1 9 10 7 2 years 1 1 2 2

30 34 2 30/07/2012 1 1 2 1 1 8 10 1 1 1

31 34 1 16/07/2012 3 1 2 1 1 7 10 8 1 1

32 45 1 20/08/2012 1 1 2 1 1 10 10 0 1 1

33 22 1 14/09/2012 1 1 1 1 1 10 10 9 1 1 2 2

34 32 2 21/03/2012 1 1 1 1 10 10 10 1 1

35 28 1 10/07/2013 1 1 1 1 10 10 8 1 1 2 2

36 62 1 03/08/2013 4 8 1 1 1 9 10 1 1 1 2 2

37 54 1 21/08/2013 3 6 2 1 1 10 10 10 1 1

38 21 1 13/09/2013 1 1 2 1 1 8 10 8 1 1

39 47 1 25/09/2013 1 1 2 1 1 5 10 7 1 1 2 2

40 19 1 16/10/2013 1 1 2 1 1 10 10 0 1 1

41 16 2 30/10/2013 1 1 2 1 1 10 10 0 1 1

42 25 1 08/01/2014 3 1 1 1 1 4 10 0 1 1

43 13 2 01/02/2014 1 1 2 1 1 8 10 7 1nd 1/2 y 1 1

44 29 2 17/02/2014 1 1 2 1 1 4 10 6 1 1

45 32 1 19/02/2014 1 1 2 1 1 5 10 8 1 1

46 35 1 24/02/2014 2 2 2 1 1 4 10 0 1 1

47 37 1 30/05/2014 1 1 2 2 1 9 10 6 1 1

48 58 1 15/09/2014 4 2 1 2 1 7 10 0 1 1

49 23 2 29/12/2014 1 1 2 2 1 10 10 8 1 1

50 54 1 06/03/2015 1 2 2 2 1 9 10 0 1 week 2 2 3 1 2

51 41 1 11/03/2015 3 1 1 2 1 12 10 0 1 week 2 2 3 1

52 20 1 11/05/2015 1 1 2 2 1 10 10 3 1 1

53 65 1 27/05/2015 3 2 2 2 1 10 10 7 1 1

54 47 2 2 1 2 2 1 10 10 7 1 1 2 2

55 28 1 13/07/2015 1 1 2 2 1 6 1 year 1 1

56 19 1 15/07/2015 1 1 2 2 1 10 10 0 1 week 2 2 3 1 2

57 43 1 27/07/2015 1 1 2 2 1 12 10 0 1 week 2 1 2 1 2

58 40 1 21/09/2015 1 2 2 2 1 10 10 0 1 week 2 2 3 1 1 Niti-S

59 41 1 05/10/2015 1 2 2 2 1 8 10 0 1 1

60 55 1 26/10/2015 1 5 2 2 1 7 10 0 1 1 2 2

61 24 1 11/11/2015 1 1 0 1 1

62 24 1 11/11/2015 1 1 2 2 1 10 10 0 1 1

63 56 1 21/11/2015 3 3 2 2 1 7 10 1 1 1

64 49 1 25/01/2016 1 5 2 2 1 10 10 6 1 1 54 50 20 45 2 2

65 57 1 22/01/2016 1 3 2 2 1 9 10 1 1 1 73 104 104 54 2 2

66 25 1 28/01/2016 3 1 1 2 1 11 10 6 1 year 1 1 250 256 20 90 2 2

67 43 2 04/04/2016 1 1 2 2 1 10 10 7 1 1

68 56 1 4 4 2 2 1 9 10 3 1 1 89 239 135 45 2 2

69 40 2 23/05/2016 1 1 2 2 1 11 10 0 1 1

70 18 1 11/05/2016 1 1 2 2 1 12 10 6 1 1

71 42 2 17/08/2016 1 1 2 2 1 12 10 0 1 1

72 45 2 03/10/2016 1 2 2 2 1 6 10 6 1 1

73 15 1 28/11/2016 1 1 2 2 1 9 10 4 6-7 month 1 1

74 40 1 12/01/2017 1 1 2 2 1 11 10 4 6-7 months 1 1

75 24 2 18/01/2017 1 1 2 2 1 11 10 4 1 1

76 29 1 03/02/2017 1 1 2 2 1 10 10 4 1 1

77 28 2 10/03/2017 1 1 2 2 1 11 10 4 1 1

78 19 1 06/03/2017 3 1 2 2 1 10 10 4 1 1

79 31 1 24/04/2017 1 1 2 2 1 12 10 4 1 1 154 148 146 132 2 2

80 40 1 08/05/2017 1 2 2 2 1 8 10 1 1 1

81 56 1 03/05/2017 1 3 2 2 1 10 10 1 1 1

82 36 1 14/06/2017 1 1 2 2 1 8 10 0 1 1

83 40 1 19/06/2017 1 1 2 2 1 9 10 1 1 1

142

lenth2 diamter3email sympt2mdoppler2mportal2mmidstent2mcavalend2mmainport2mvenogram2mballoon2mnewstent2msympt4mdoppler4mportal4mmidstent4mcavalend4mmainport4mvenogram4mballoon4mnewstent4mtelephonesympt7mdoppler7mportal7mmidstent7mcavalend7mmainport7m

1 1 1 1 1 1

1 1 2 2 161 3 1 2

1 1 1 1 133 157 201 75 1 1

1 1 1 1 2 1

1 1 140 166 1 1 1 1

1 1 2 3 111 30 2 1 2

1 1 1 1 112 110 90 56 2 2 1 1

1 1 110 123 130 2 2

1 1 1 1 1 1 142 90 144

1 1 142 100 2 2

1 1 1 1 1 1

1 1 1 1 1 1 184 135 150 30

1 1 1 1 1 1

1 1 1 1 100 20 2 2 1 1

1 1 1 1 1 1 96 121 120

1 1 1 1 2 1 219 145 142

1 1 1 1 197 97 98 50 2 2 1 1

1 1 1 1 1 1

1 1 1 1 59 79 108 2 2 1 1

1 1 1 1 1 1

1 1 1 1 1 1 130 120 110

1 1 1 2 2 1

1 1 1 1 1 1 255 246 151

1 1 1 1 80 107 114 2 2 1 1

1 1 1 1 1 1

1 1 1 1 1 1

1 1 106 99 65 2 2

1 1 108 96 107 48 2 2 1 1 1 1

1 1 1 1 1 1

1 1 1 1 105 106 81 34 2 1 1 1

1 1 1 1 1 1

1 1 1 1 1 1 95 119 127 54

1 1 1 1 1 1 170 157 159 50

1 1 1 1 204 143 203 54 2 2 1 1

1 1 1 1 1 1 114 100 91 54

1 1 1 1 98 101 112 43 2 2

1 1 1 1 1 1 173 216 179 45

1 1 1 1 1 1

1 1 1 1 1 1

10 10

1 1 1 1

1 1 1 1 94 100 112 75 2 1 1 1 78 90 100 34

1 1 93 96 48 48

1 1 1 1 1 1

1 1 110 142 122 40 2 2 1 1 1 1

1 1 1 1 125 270 175 45 2 2

1 1 1 1 1 1

1 1 1 1 178 116 168 60 2 1 1 1 123 178 123 40

1 1 1 1 1 1 136 156 280 45

1 1 1 1 2 2

1 1 1 1 1 1 98 100 90 45

1 1 1 1 1 1 111 100 94 35

1 1 1 1 asymtomatic, no doppler scan1 1

1 1 1 1 1 1 112 94 98 34

1 1 1 1 130 136 143 78 2 2 1 1 122 130 127 73

1 1 200 210 210 50 2 2

1 1 153 220 236 77 2 2 1 1 1 1 223 215 230 72

new symt, velcoties not mentioned3 1

143

venogram7mballoon7mnewstent7msympt13mdoppler13mportal13mmidstent13cavalend13mainport13venogram13balloon13mnewstent13sympt18mdoppler18mportal18mmidstent18cavalend18mainport18venogram18balloon18mnewstent18telinf sympt2ydoppler2yportal2ymidstent2ycavalend2y

1 1 1 1 3 1 100

1 2 3 1 1

2 3 2

1 1 1 1 1 1 112 120 112

1 1 1 1 1 1

2 2 1 1 136 148 106 55 2 2 1 1 1 1 81 80 117

1 1 1 1 no symtomps, imaging not available1

2 2 1 1 184 160 150 30 2 2 1 1 1 1 165 179 157

1 1 108 154 120 2 2 1 1 1 1 144 115 111

1 1 120 90 100 24 2 2 1 1 1 1

2 2 1 1 110 143 115 2 2 1 1 1 1 139 149 104

4 2 2 2 3 220 160 140 24 2 1 2

1 1 151 136 99 51 2 2

1 1 119 102 116 32 2 2 1 1 1 1 91 184 144

1 1 52 71 41 2 2 1 1 3 1 41 45 46

1 1 131 120 141 54 2 2 1 1 157 132 150 50 2 2 1 1

4 2 2 1 1 131 121 130 2 2 1 1 3 2

1 2 2

2 2 1 1 169 207 149 2 1 1 1 1 1 110 203 153

1 1 80 110 114 2 2 1 1 1 1 140 128 118

1 1 101 50 75 86 2 2 1 1 1 1

1 1 1 1 1 1 105 184 101

1 1 1 1 1 1

1 1 1 1 1 1

1 1 105 106 81 37 2 1 1 1 1 1

1 1 3 3 2 1 2

3 2 1 1 155 114 91 36

2 2 1 1 129 148 176 25 2 2 1 1 1 1 140 150 60

1 3 172 276 166 163

2 2 1 1 1 1

1 1 100 120 141

2 2 1 1 172 172 144 40 2 2 1 1 1 1 86 90 92

1 1 210 180 176 36 2 2 1 1 1 1 220 180 190

2 2 2 1 2

4 2 2 1 1 2 2

2 2 3 1 2

1 1 1 1 1 1 134 117 159

1 1 90 100 120 53 2 2

4 2 2 1 1 90 100 110 43 2 2

2 1 2

3 1 2

2 2

2 2

2 2

2 2

2 2

144

mainport2yvenogram2yballoon2ynewstent2ysympt3ydoppler3yportal3ymidstent3ycavalend3ymainport3yvenogram3yballoon3ynewstent3ysympt4ydoppler4yportal4ymidstent4ycavalend4ymainport4yvenogram4yballoon4ynewstent4ytelinf1 sympt5ydoppler5yportal5ymidstent5y

4 3 2 2 2 3 1 2

4 2 2 1 1 1 1 111 106 108 47 1 1

1 1 100 90 96 43 2 2

55 4 2 2 1 1 75 96 109 4 2 2 1 1 1 1

39 2 2 3 3 2 1 2

78 1 1 114 115 111 78 2 2 1 1 193 155 151 52 2 2 1 1 152 117

1 1 2 2 1 1 1 1

32 2 2 1 1 110 143 115 1 1 1 1 90 130 120 23 1 2 2 1 1

32 2 2 1 1 60 101 120 24 2 2

2 1 2

3 1 2

no symtoms till 5 yrs no usg/dopler done

2 2 1 1 169 207 149 2 2

40 2 2 1 1 1 1 42 87 81 16

1 1 1 1 1 1 97 111

46 2 2 1 1 108 100 85 2 2

1 1 1 1 outside report email, no velocities1 1

3 3 20 21 35 21 4 3

2 2

50 2 2 1 1 102 95 162 40 2 2

1 1 121 129 172 72

34 4 2 2

36 2 2

34 4 2 2

70 2 2

145

cavalend5ymainport5yvenogram5yballoon5ynewstent5ysympt6ydoppler6yportal6ymidstent6ycavalend6ymainport6yvenogram6yballoon6ynewsten6ysympt7ydoppler7yportal7ymidstent7ycavalend7ymainport7yvenogram7yballoon7ynewsten7ysympt11ydoppler11yportal11y

1 1 1 1 1 1 78

1 1 77 87 76 47 4 2 2

1 1 109 93 99 2 2 1 1 93 95 99 46 4 2 2

104 11 2 2 1 1 115 146 114 41 2 2

1 1 70 100 112 42 1 2 2

2 2 1 1 4 2 2

no symtoms till 5 yrs no usg/dopler done

108 46 2 2

2 2

146

midstent11cavalend11mainport11venogram11balloon11ynewstent11ballangiosymptbadopplerbaportalbamidstentbacavalendbamainportbavenogrambaballoonbalostfollowfollowtillother death deathcause

1

89 97 27 4 2 2

1 0 1 death in 2014, exact cause not kown, documents NA.

1 1 Phonic information, death in 2014,cause uncertain, documents NA

1

1 0

1 0

3

1 death on day 4 post TIPS, Liver ischemia/infarction

liver transplat

0 1 gagrene bowel, operated, death on post op day 1

1 operted for intestinal obstruction, post op unstable- death

1 on day 3 post TIPS, spontaeous bcterial peritoitis, AKI

liver trasplant 3mon post tips

1 day 2 post TIPS, hypotension during TIPS, worsened

147

slno age sex ballangionoba batime ballfup sympt doppler portal midstentcavalendmainportvenogramballoon newstentsympt2mdoppler2mportal2mmidstent2mcavalend2mmainport2m

1 45 1 1 2 post 1st BA thrombosed at 6 monnths, 2nd BA not done 5 1 1

2 28 2 1 3 6 months 11 1 1 3 2

3 34 2 1 3 1 year, 2 year and 3 year 7 1 1 2 2 1 1

4 45 1 1 1 5 month 5 1 1 1 1 141 119 201 45

5 20 1 1 2 1st at 3 years, 2nd at 5th years(2 years after 1st BA 7 1 1

6 15 1 1 1 1 and half year 1 1 1

7 24 2 1 3 1st at 3y,2nd at 1yr(postBA),3rd at 2 yrs(post 2 BA) 10 1 1 1 1

8 13 2 1 3 1st at 1 and half year,2nd 2 mont(postb), 3rd 1y postba 7 1 1 3 3

9 54 1 1 1 15th day 1 1 1

10 54 1 1 1 1st week 7 1 1 1 1

11 30 1 1 6 1 year 5 1 1 1 1

12 19 2 1 1 1st week 5 1 1 2 2 1 1

13 43 1 1 1 1st week 4 1 1 1 1

14 25 1 1 1 1 year 1 1 1

15 15 1 1 1 1 year 1 1 1

16 10 1 1 1 1 year 1 1 1 123 135 131 28 2 2

venogram2mballoon2mnewstent2msympt4mdoppler4mportal4mmidstent4mcavalend4mmainport4mvenogram4mballoon4mnewstent4msympt7mdoppler7mportal7mmidstent7mcavalend7mmainport7mvenogram7mballoon7mnewstent7msympt13mdoppler13mportal13mmidstent13cavalend13mainport13venogram13balloon13m

1 1 3 2 4 3 2

3 1 2

1 1 1 1 3 3 130 125 200 18 2 1

2 2 1 1 1 2 2 1 1 1 1 1 2

1 1 2 2 1 1 41 42 36 23 2 2 1 1 31 56 136 12 2

1 1 1 1 1 3 120 160 220 34 3 1

2 1 2

1 1 2 2 1 1 56 100 50 26 2 2 1 3 65 46 297 17 2 3

1 1 1 3 3 2 2 3 70 212 117 60 2 1

2 2 1 1 1 1 3 3 3

1 1 1 1 93 137 135 47 2 2

newstent13sympt18mdoppler18mportal18mmidstent18cavalend18mainport18venogram18balloon18mnewstent18sympt2ydoppler2yportal2ymidstent2ycavalend2ymainport2yvenogram2yballoon2ynewstent2ylostfollowfollowtilldeath deathcausetelphone sympt3ydoppler3y

2

2

2 1 1 46 45 41 30 2 2 3 3

asymtomatic, Dopper normal

2

2 1 1 1 1 42 65 297 15 2 2

2

148

portal3ymidstent3ycavalend3ymainport3yvenogram3yballoon3ynewstent3ysympt5ydoppler5yportal5ymidstent5ycavalend5ymainport5yvenogram5yballoon5ynewstent5ylostfollo1followtil1death1 deathcaus1sympt11ydoppler11yportal11ymidstent11cavalend11mainport11venogram11balloon511newstent11

2 1 1

2 1

lostfollo2followtil2ballangio2symptbadopplerbaportalbamidstentbacavalendbamainportbavenogrambaballoonbaballfup1sympt1 doppler1portal1 midstent1cavalend1mainport1venogram1balloon1newstent1sympt2m1doppler2m1portal2m1midstent21cavalend21mainport21venogram21balloon2m1

2

1 1 1 2 1 1 69 79 100 62 2 2 1 1 109 173 100 36 2

1 1 1 1 1

1 1 1 1 1 1 1

1 1 1 1 1 1 1

1 1 1 1 1 1 1

1 1 1 2 3 46 259 94 29 2 1

1 1 1

newstent21sympt4m1doppler4m1portal4m1midstent41cavalend41mainport41venogram41balloon4m1newstent41sympt7m1doppler7m1portal7m1midstent71cavalend71mainport71venogram71balloon7m1newstent71sympt13m1doppler131lostfolupportal13m1midstent14cavalend14mainport14venogram14balloon131newstent14

2 3 3 28 30 24 1 2

1 1 3 3 202 181 180 22 2 1 1

1 1 1 1 1 1

1 1 1 1 3 3 160 130 360 35 2 1 2

1 1 1 1 3 3 2 1 2

2

3 2 1

149

stenttypelength diametersympt18m1doppler181portal18m1midstent19cavalend19mainport19venogram19balloon181newstent19sympt2y1doppler2y1portal2y1midstent22cavalend22mainport22venogram22balloon2y1newstent22lostfollo3followtil3death2 deathcaus2ballangio3symptba1dopplerba1portalba1

1

Viator Gor 10 10 1 1 1 134

1 1 2 3 60 70 180 20 2 1 2

1 1 2 3 200 360 180 27 2 1 2 1

1 1 1

1

mainport42venogram42balloon4m2newstent42sympt7m2doppler7m2portal7m2midstent72cavalend72mainport72venogram72balloon7m2newstent72sympt13m2doppler132portal13m2midstent15cavalend15mainport15venogram15balloon132newstent15sympt18m2doppler182portal18m2midstent20cavalend20mainport20venogram20balloon182newstent20sympt2y2

1 1 141 100 90 43 2 2

1 1 119 159 220 2 2

53 2 1 2